Untitled - Red Temática de investigación cooperativa en cáncer

Programa Científico 7
Resumenes de Comunicaciones Orales 15
Listado de Posters 37
Resumenes de Posters 43
Listado de Ponentes 93
© 2012 Red Temática de Investigación Cooperativa en Cáncer
Imprime: Jet Print SL
Diseño y maquetación: Detrazos Diseño e Internet
www.detrazos.es
5

Lugar: Salón de Actos del Pabellón Docente del Hospital Vall d’Hebron
Paseo Vall d’ Hebron 119 - 129 08035 Barcelona - España
7

10:00 h Recepción de los Participantes
10:00 h Montaje de Pósters
10:30 h Inauguración
Dr. Antonio L. Andreu Périz / Subdirector General de Evaluación y Fomento de la
Investigación del Instituto de Salud Carlos III (ISCIII)
Dr. José Jerónimo Navas / Gerente del Hospital Vall d’Hebron
Dr. Joan Comella / Director del Vall d’Hebron Institut de Recerca (VHIR)
Dr. Eugenio Santos / Centro de Investigación del Cáncer de Salamanca y Coordinador
Nacional de la Red Tematica de Investigación Cooperativa en Cáncer (RTICC)
Dr. Luis Montuenga / Centro de Investigación Médica Aplicada (CIMA), Universidad de
Navarra y Coordinador del Programa de Formación y Movilidad de la RTICC
Dr. Jaume Reventos / Unidad de Investigación Biomédica y Oncología Traslacional i
Pediátrica del Vall d’Hebron Institut de Recerca (VHIR)
11.00 h. Conferencia Inaugural
“IDENTIFICATION OF NOVEL DRIVER MUTATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA THROUGH WHOLE
GENOME SEQUENCING”
Dr. Xose S. Puente
Department of Biochemistry, University of Oviedo
12:00 h Descanso / Coffee Break
Lunes 19 de Noviembre
12:50 h O-02. “p21 LOSS INDUCES AN INFLAMMATORY SKIN DISEASE AND SPONTANEOUS
TUMOR DEVELOPMENT IN MICE BEARING EPIDERMAL SPECIFIC pRb ABLATION”
Cristina Saiz Ladera / Centro de Investigaciones Energéticas, Medioambientales y
Tecnológicas (CIEMAT), Madrid
Grupo RTICC: RD06/0020/0029
13:10 h O-03. “DOWN-REGULATION OF FOXP1 IS REQUIRED DURING GERMINAL CENTER B CELL
FUNCTION”
Aitziber Ainara Sagardoy Rodrigo / Centro de Investigación Médica Aplicada (CIMA),
Pamplona
Grupo RTICC: RD06/0020/0088
13:30 h O-04. “EPIGENETIC PROFILE IN CHRONIC LYMPHOCYTIC LEUKEMIA USING
METHYLATION-SPECIFIC MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION”
Ana Mª Cosialls Castel / Instituto de Investigación Biomédica de Bellvitge (IDIBELL)-
Universitat de Barcelona, Barcelona
Grupo RTICC: RD06/0020/0097
13:50 h O-05. “CRYPTIC DUPLICATIONS AND DELETIONS TO IMPROVE RISK GROUPS IN
CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA”
Elixabet López López / Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU),
Lejona (Vizcaya
Grupo RTICC: RD06/0020/0048
14:10 h O-06. “CCND2 REARRANGEMENTS ARE THE MOST FREQUENT GENETIC EVENTS IN
CYCLIN D1-NEGATIVE MANTLE CELL LYMPHOMA”
Cristina Royo Moreno / Hospital Clínic -IDIBAPS, Barcelona
Grupo RTICC: RD06/0020/0039
Sesión mañana
14:30 h Comida
Moderadores: Dra. Dolors Colomer / Hospital Clínic-IDIBAPS
Dr. Andreas Doll / Institut de Recerca-Hospital Universitari Vall d’Hebron
15:30 h Sesión de Pósters
12:30 h O-01.“THE MULTI-KINASE INHIBITOR SORAFENIB BLOCKS MIGRATION, BCR SURVI-
VAL SIGNALS, PROTEIN TRANSLATION AND STROMA-MEDIATED BORTEZOMIB RESISTANCE IN
MANTLE CELL LYMPHOMA”
Sílvia Xargay Torrent / Hospital Clínic-IDIBAPS, Barcelona
Grupo RTICC: RD06/0020/0014
8 9

Sesión de Tarde
Moderadores: Dr. Joan Gil / Instituto de Investigación Biomédica de Bellvitge (IDIBELL)
Dra. Mireia Olivan / Institut de Recerca-Hospital Universitari Vall d’Hebron
16:50 h O-07. “A DOMINANT-NEGATIVE N-TERMINAL FRAGMENT OF HER2 FREQUENTLY
EXPRESSED IN BREAST CANCERS”
Beatriz Morancho Armisen / Vall D’Hebrón Institut D’Oncologia (VHIO), Barcelona
Grupo RTICC: RD06/0020/0022
17:10 h O-08. “MITOTIC ARREST DOWN-REGULATES FLIP EXPRESSION AND SENSITIZES
TUMOR CELLS TO THE EXTRINSIC PATHWAY OF APOPTOSIS”
Tania Sánchez Pérez / Centro Andaluz de Biología Molecular y Medicina Regenerativa
(CABIMER), Sevilla
Grupo RTICC: RD06/0020/0068
17:30 h O-09. “microRNA-BASED THERAPY FOR HIGH-RISK NEUROBLASTOMA”
Aroa Soriano Fernández / Institut de Recerca Hospital Universitari Vall d’Hebron,
Barcelona
Grupo RTICC: RD06/0020/1021
17:50 h O-10. “INFLUENCE OF LKB1/STK11 IN GENE EXPRESSION PATTERNS INDUCED BY
ENERGY STRESS IN LUNG CANCER CELL LINES”
Rossana Gonçalves Restani / Instituto de Investigación Biomédica de Bellvitge (IDIBELL),
Barcelona
Grupo RTICC: RD06/0020/0062
18:10 h O-11. “IDENTIFICATION OF DIFFERENTIAL GENOMIC AND PROTEOMIC PROFILES
ASSOCIATED WITH BONE METASTASES IN PROSTATE CANCER”
Marta Garcia López / Institut de Recerca-Hospital Universitari Vall d’Hebron, Barcelona
Grupo RTICC: RD06/0020/0058
18:30 h O-12. “DIOXIN RECEPTOR CONTROLS CSK-BINDING PROTEIN SIGNALING TO CAVEOLIN
1 AND Β1 INTEGRIN TO MODULATE CELL ADHESION AND MIGRATION”
Martes 20 de Noviembre
Sesión de Mañana
Moderadores:
Dr. Francesc Sole Ristol / Institut de Recerca Contra la Leucèmia Josep Carreras (IJC)
Dra. Marina Rigau / Institut de Recerca-Hospital Universitari Vall d’Hebron
09:10 h O-13. “CD44 POSITIVITY CONFERS RESISTANCE TO SORAFENIB-INDUCED CELL DEATH
IN HEPATOCELLULAR CARCINOMA (HCC) CELLS”
Joan Fernando Peidró / Instituto de Investigación Biomédica de Bellvitge (IDIBELL),
Barcelona
Grupo RTICC: RD06/0020/0097
09:30 h O-14. “ANALYSIS OF NEW GENES DIRECTLY REGULATED BY FOXE1 IN THYROID CELLS”
Lara Paula Fernández Álvarez / Instituto de Investigaciones Biomédicas “Alberto Sols” IIB,
Madrid
Grupo RTICC: RD06/0020/0060
09:50 h O-15. “MOLECULAR SUBSETS OF MANTLE CELL LYMPHOMA DEFINED BY THE IGHV MUTA-
TIONAL STATUS AND SOX11 EXPRESSION HAVE DISTINCT BIOLOGICAL AND CLINICAL FEATURES”
Alba Navarro Lopez / Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona
Grupo RTICC: RD06/0020/0039
10:10 h O-16. “ETV5 AND FOXM1 TRANSCRIPTION FACTORS ARE OVEREXPRESSED IN OVARIAN
CANCER AND REGULATE CELLULAR ADHESION AND PROLIFERATION CONTRIBUTING TO TUMOR
DISSEMINATION”
Marta Llauradó Fernández / Institut de Recerca-Hospital Universitari Vall d’Hebron,
Barcelona
Grupo RTICC: RD06/0020/0058
10:30 h O-17. “COUNTERACTING AUTOPHAGY OVERCOMES RESISTANCE TO EVEROLIMUS IN
MANTLE CELL LYMPHOMA”
Laia Rosich Moya / Hospital Clínic-IDIBAPS, Barcelona
Grupo RTICC: RD06/0020/0014
Javier Rey Barroso / Universidad de Extremadura, Badajoz
Grupo RTICC: RD06/0020/1016
18:50 h Fin de las Sesiones
10:50 h O-18. “PIK3CA ALTERATIONS IN BLADDER CANCER RECURRENCE”
Mónica Martínez Fernández / Centro de Investigaciones Energéticas, Medioambientales y
Tecnológicas (CIEMAT), Madrid
Grupo RTICC: RD06/0020/0029
10 11

11:10 h O-19. “PAPEL DEL CORREPRESOR NcoR EN LA INHIBICIÓN DE LA INVASIVIDAD Y FOR-
MACIÓN DE METÁSTASIS POR TR”
Olaia Antia Martinez Iglesias / Instituto de Investigaciones Biomédicas “Alberto Sols” IIB,
Madrid
Grupo RTICC: RD06/0020/0036
11:30 h O-20. “DIFFERENTIAL FUNCTIONS OF EVI1 SPLICE ISOFORMS IN CELL VIABILITY AND
TRANSCRIPTIONAL REGULATION. THE EVI1 HUMAN PROTEIN REGULATES ITS OWN TRANSCRIP-
TION”
Miren Maicas Irigaray / Centro de Investigación Médica Aplicada (CIMA), Pamplona
Grupo RTICC: RD06/0020/0078
12:00 h Descanso / Coffee Break
12:00 h Retirada de Pósters
12.30 h. Conferencia Coordinador Nacional de la RTICC
Dr. Eugenio Santos / Coordinador Nacional de la RTICC, Centro de Investigación del Cáncer
de Salamanca
12:40 h / Entrega PREMIO DE INVESTIGACIÓN COOPERATIVA EN ONCOLOGÍA RTICC
2012
12:50 h / Exposición del galardonado con el PREMIO DE INVESTIGACIÓN COOPERATI-
VA EN ONCOLOGÍA RTICC 2012
13:35 h / Clausura
Dr. Eugenio Santos / Centro de Investigación del Cáncer de Salamanca
Dr. Luis Montuenga / Centro de Investigación Médica Aplicada (CIMA), Universidad de
Navarra
Dr. Jaume Reventos / Unidad de Investigación Biomédica y Oncología Traslacional i Pediátrica
del Vall d’Hebron Institut de Recerca (VHIR)
CONFERENCIA MAGISTRAL
IDENTIFICATION OF NOVEL DRIVER MUTATIONS IN CHRONIC LYMPHOCYTIC
LEUKEMIA THROUGH WHOLE GENOME SEQUENCING
XOSE S. PUENTE
DEPARTMENT OF BIOCHEMISTRY, UNIVERSITY OF OVIEDO
Chronic lymphocytic leukemia (CLL), the most frequent leukemia in adults in Western countries,
is a B-cell neoplasm clinically and biologically very heterogeneous. The differences
in the behavior of the disease have been associated with two major molecular subtypes
characterized by high and no or low number of somatic mutations in the variable region of
immunoglobulin genes (IGHV-mutated and IGHV-unmutated, respectively). However, the
genetic and molecular alterations leading to the development and progression of the disease
are still poorly understood. The aim of the CLL Cancer Genome Consortium is to generate
a comprehensive catalogue of genetic alterations relevant to the pathogenesis and clinical
evolution of the disease using next generation sequencing combined with other genomic
technologies in a large series of well characterized tumors.
We have completed the sequencing and analysis of 109 cases of CLL using either whole
genome sequencing (4 cases) or whole exome sequencing (105 cases). This has led us to
the identification of about 1,000 somatic mutations per tumor genome in non-repetitive
regions, and a median of 45 somatic mutations per case when using exome sequencing.
Interestingly, IGHV-mutated tumors had more protein-altering mutations than CLL tumors
without mutations in the IGHV region, as well as an increased number of A>C/T>G transversions.
In addition, global analysis of these data resulted in the identification of 78 genes
which are recurrently mutated in CLL. They include NOTCH1 and SF3B1, which are mutated
in more than 10% of cases, or POT1, CHD2 and LRP1B, mutated in about 5% of tumors.
There is a clear difference in the frequency of these mutations between IGHV-mutated
and IGHV–unmutated CLL tumors, extending at the genomic level the clinical differences
observed in these two CLL subtypes. Together with SF3B1, which encodes a subunit of the
spliceosomal U2 small nuclear ribonucleoprotein, at least 30 genes involved in RNA maturation
have mutations in CLL, suggesting that RNA splicing and maturation might constitute
an important mechanism driving this disease. Finally, further analysis of more than 250 CLL
cases showed that patients with mutations in either NOTCH1 or SF3B1 had faster disease
progression and shorter overall survival. Together, these data illustrate the heterogeneity
of the disease and the utility of genome-wide studies to identify the molecular mechanisms
driving the development of CLL.
This project is funded by the Spanish Ministry of Science and Innovation through the Institute
of Health Carlos III.
12 13

O-01
THE MULTI-KINASE INHIBITOR SORAFENIB BLOCKS MIGRATION, BCR SURVIVAL
SIGNALS, PROTEIN TRANSLATION AND STROMA-MEDIATED BORTEZOMIB RESIS-
TANCE IN MANTLE CELL LYMPHOMA
XARGAY-TORRENT S 1 , LÓPEZ-GUERRA M 1 , SABORIT-VILLARROYA I 2 , ROSICH L 1 , NAVARRO A 2 ,
VILLAMOR N 1 , AYMERICH M 1 , PÉREZ-GALÁN P 1 , ROUÉ G 1 , CAMPO E 2 , COLMER D 1
1
HOSPITAL CLÍNIC-IDIBAPS (RD06/0020/0014)
2
HOSPITAL CLÍNIC-IDIBAPS (RD06/0020/0039)
Mantle cell lymphoma (MCL) is a B-lymphoma harboring the t(11;14)(q13;q32) translocation
which leads to the overexpression of cyclin D1, and is characterized by bad prognosis
and an aggressive course. Unfortunately, current therapies have shown limited efficacy and
relapses occur early, thus our purpose was to evaluate the antitumoral properties of the
multikinase inhibitor sorafenib in MCL.
We analyzed the effects of sorafenib in 9 MCL cell lines and 17 primary MCL samples, where
sorafenib induced a time- and dose-dependent apoptosis. Both in cell lines and primary MCL
cells, sorafenib induces rapid dephosphorylation of the BCR (B-Cell Receptor)-associated
tyrosine kinases, SYK and LYN, as well as of FAK, a downstream SRC target involved in focal
adhesion. In line with this, we demonstrate a strong synergy when combining sorafenib
with the SYK inhibitor, R406. In parallel, we show that sorafenib also blocks Mcl-1 and cyclin
D1 translation, which promotes an unbalance between pro- and anti-apoptotic proteins
and facilitates the release of Bax from cyclin D1. This process leads to the induction of the
mitochondrial apoptotic pathway and caspase-dependent and independent mechanisms.
Moreover, sorafenib inhibits MCL cell migration as well as actin polymerization in response
to CXCL12. FAK siRNA-mediated knockdown partially prevents this inhibitory effect, indicating
that FAK is a relevant target for the action of sorafenib in MCL cells. Importantly,
this compound resensitizes MCL cells cocultured with bone marrow-derived stromal and
follicular dendritic-like cells to bortezomib-induced apoptosis, thus sorafenib antagonizes
stroma-mediated resistance in MCL.
In conclusion, we provide first evidence on the molecular mechanism of action of sorafenib
in MCL. We propose that this compound inhibits cell migration and stroma-mediated bortezomib
resistance by interfering BCR signaling and protein translation. These results suggest
that sorafenib, alone or in combination with bortezomib-based therapies, may represent a
promising approach for the treatment of MCL patients.
Observaciones:
Research funding
This work was supported in part by grants RD06/0020/0014 from Red Temática de Investigación
Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish
Ministry of Economy and Competitiveness and SAF 09/9503 to D.C. S.X-T. is a recipient of
predoctoral fellowship from Spanish Ministry of Science and Education (FPU) and M.L-G.
holds a contract from Fundación Científica de la Asociación Española contra el Cáncer.
17

O-02
p21 LOSS INDUCES AN INFLAMMATORY SKIN DISEASE AND SPONTANEOUS TU-
MOR DEVELOPMENT IN MICE BEARING EPIDERMAL SPECIFIC pRb ABLATION
SAIZ-LADERA C 1 , LARA MF, GARÍN M 1 , RUIZ S, SANTOS M 1 , LORZ C 1 , GARCIA ESCUDERO R 1 ,
BRAVO A 2 , FERNANDEZ-CAPETILLO O 3 , SEGRELLES C 1 PARAMIO J 1
1
CENTRO DE INVESTIGACIONES ENERGÉTICAS, MEDIOAMBIENTALES Y TECNOLÓGICAS (CIEMAT),
MADRID (RD06/0020/0029)
2
FACULTAD DE VETERINARIA, USC
3
CENTRO NACIONAL DE INVESTIGACIONES ONCOLÓGICAS (CNIO), MADRID
The ablation of the retinoblastoma gene product in epidermis results in hyperplasia and
hyperkeratosis, due to increased proliferation and altered differentiation, but not to sporadic
tumors.
Given the wide functions of p21 in epidermis and the fact that p21 can control proliferation
and differentiation, even in the absence of pRb, we have now generated mice doubly
deficient in pRb and p21 (pRb Epi p21-/-). In these mice, we found that p21 compensates
for some of the effects observed in the absence of pRb, as the phenotypic abnormalities
of Rb-deficient epidermis become more severe with the consecutive loss of Cdkn1a alleles.
In addition, we also observed the development of an inflammatory phenotype and the
spontaneous development of tumors of epithelial origin, in particular affecting oral tissues.
Gene profiling studies in conjunction with biochemical analyses revealed changes affecting
p53 and DNA damage response in pRb Epi p21-/- mouse skin, and identified a significant
overlap between deregulated genes in mouse and human squamous cancers.
Our findings support a model in which pRb, in conjunction with p21, plays a central role
in regulating multiple epithelial processes leading to specific tumor suppressor functions.
O-03
DOWN-REGULATION OF FOXP1 IS REQUIRED DURING GERMINAL CENTER B CELL
FUNCTION
SAGARDOY A 1 , MARTÍNEZ-FERRANDIS J 1,2 , ROA S 1 , BUNTING K 2 , AZNAR A 1 , ELEMENTO O 2 ,
SHAKNOVICH R 2 , FONTÁN L 1 , FRESQUET V 1 , ROBLES EF 1 , SAGAERT X 3 , MELNICK A 2 , MARTÍNEZ-
CLIMENT JA 1
1
CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA),PAMPLONA (RD06/0020/0088)
2
WEILL CORNELL MEDICAL COLLEGE NY (USA)
3
UNIVERSITY OF LEUVEN, BEGIUM
B cell maturation, germinal center (GC) formation and terminal differentiation are dependent
on the interplay between BCL6 and other key transcriptional regulators. Forkhead box
protein 1 (FOXP1) is a transcription factor that coordinates transitions between differentiation
stages at early B cell development. FOXP1 expression has been associated with poor
prognosis in patients with diffuse large B cell lymphoma (DLBCL), but whether it plays a
role in mature B cells is unknown.
Analyses of human tonsilar B cell subpopulations helped us to reveal that FOXP1 shows
opposite expression pattern to BCL6, suggesting that FOXP1 may play a role during late
B cell development in the course of B cell activation and GC formation. Chromatin immunoprecipitation
and gene expression assays on human tonsilar samples and DLBCL cells
indicated that FOXP1 may act as both a transcriptional activator and repressor of a network
of genes typically involved in the GC reaction, half of which are also BCL6 targets.
To study FOXP1 function in vivo, we developed transgenic mice expressing human
FOXP1 in the lymphoid lineage. These mice exhibited irregular expansion of GCs in the
spleen, showing a moderate increase in naïve (B220 + IgM hi IgM hi/lo ) and marginal-zone B
cells (B220 + CD21 + CD23 - ) that was accompanied by a significant decrease in GC B cells
(B220 + Fas + PNA hi /GL7 hi ).
Furthermore, aberrant expression of FOXP1 impaired the transcription of non-coding 1
germline transcripts (GLTs) and inhibited efficient class-switching to the IgG1 isotype.
Taken together, these studies reveal that FOXP1 is physiologically down-regulated in GC B
cells and that aberrant expression of FOXP1 may impair the mechanisms triggered by B
cell activation, potentially antagonizing some of the actions of BCL6 during the regulation
of the GC reaction.
18 19

O-04
EPIGENETIC PROFILE IN CHRONIC LYMPHOCYTIC LEUKEMIA USING METHYLA-
TION-SPECIFIC MULTIPLEX LIGATION-DEPENDENT PROBE AMPLIFICATION
COSIALLS AM 1 , SANTIDRIÁN AF 1 , COLL-MULET LL 1 , IGLESIAS-SERRET D 1 , GONZÁLEZ-GIRONÈS
DM 1 , PÉREZ-PERARNAU A 1 , RUBIO-PATIÑO C 1 , GONZÁLEZ-BARCA E 2 , ALONSO E 3 , PONS G 1 , GIL J 1
1
DEPARTAMENT DE CIÈNCIES FISIOLÒGIQUES II, INSTITUT D’INVESTIGACIÓ BIOMÈDICA DE BELL-
VITGE (IDIBELL)-UNIVERSITAT DE BARCELONA, L’HOSPITALET DE LLOBREGAT, BARCELONA, SPAIN
(RD06/0020/0097)
2
DEPARTAMENT D’HEMATOLOGIA CLÍNICA, IDIBELL-INSTITUT CATALÀ D’ONCOLOGIA, L’HOSPITALET
DE LLOBREGAT, BARCELONA, SPAIN (RD06/0020/1040)
3
SERVEI D’HEMATOLOGIA, IDIBELL-HOSPITAL DE BELLVITGE, L’HOSPITALET DE LLOBREGAT, BAR-
CELONA, SPAIN
Aims: The contribution of epigenetic silencing mechanisms in the pathogenesis of chronic
lymphocytic leukemia (CLL) has gained importance in recent years. However, the methods
used so far are labor intensive which makes it difficult to implement the methylation status
assessment in clinical practice. Here we analyze the methylation status of 35 tumor suppressor
genes using methylation-specific multiplex ligation-dependent probe amplification
(MS-MLPA) in CLL.
Materials & Methods: DNA of 37 samples from patients with CLL, 6 healthy donors and
Jurkat and Ramos cells lines was analyzed by MS-MLPA.
Results: Our results confirm that hypermethylation is a common and not randomly distributed
event in CLL, and some genes like WT1, CDH13, IGSF4/TSLC1, GATA5, DAPK1 or
RARB are hypermethylated in more than 25% of the analyzed samples. Importantly, MS-
MLPA also detected hypermethylation of some genes not reported previously in CLL, and
their methylation status was confirmed by bisulfite sequencing.
Conclusions: These results indicate that MS-MLPA is a useful technique for the detection
of methylation in CLL samples with automated data processing at a low cost per sample.
Selecting CLL-specific methylation targets in order to generate a CLL-specific MS-MLPA
probe set could enhance its usefulness as a tool in studies of risk stratification and guiding
the best therapeutic decision.
Observaciones: Este trabajo se ha realizado en colaboración entre los grupos de la
RTICC del Dr. Joan Gil Santano y la Dra. Eva María González Barca (códigos de grupo
RD06/0020/0097 y RD06/0020/1040).
O-05
CRYPTIC DUPLICATIONS AND DELETIONS TO IMPROVE RISK GROUPS IN CHILD-
HOOD ACUTE LYMPHOBLASTIC LEUKEMIA
LÓPEZ-LÓPEZ E 1 , PUIGGROS A 2 , PIÑAN MA 3 , NAVAJAS A 4 , SOLÉ F 2 , GARCÍA-ORAD A 1
1
DEPARTMENT OF GENETICS, PHYSIC ANTHROPOLOGY AND ANIMAL PHYSIOLOGY, UNIVERSITY OF THE
BASQUE COUNTRY, BILBAO (RD06/0020/0048)
2
GROUP OF TRANSLATIONAL RESEARCH IN HEMATOLOGIC NEOPLASIAS, IMIM HOSPITAL DEL MAR,
BARCELONA (RD07/0020/2004)
3
DEPARTMENT OF HEMATOLOGY AND HEMOTHERAPY, UNIVERSITY HOSPITAL CRUCES, BILBAO
(RD06/0020/0048)
4
DEPARTMENT OF ONCOHEMATOLOGY, UNIVERSITY HOSPITAL CRUCES, BILBAO (RD06/0020/0048)
Acute lymphoblastic leukemia (B-ALL) is the most common pediatric malignancy and a
major cause of death by disease in children. Survival has increased adapting therapy to risk
groups, characterized by prognostic markers that include cytogenetic alterations. Therapy
is intensified in higher risk patients. However, some patients do not respond properly to
treatment and have to be moved to higher risk groups. This could mean that the risk groups
are not well defined, due in part to undetected cryptic alterations. Therefore, in this study
we wanted to identify novel cryptic deletions and duplications that could allow the recognition
of the patients that may be receiving less treatment than they need.
Methods
We analyzed DNA samples from 23 patients diagnosed with B-ALL from the different risk
groups (7 standard risk, 10 high risk, 1 very high risk, and 5 that changed risk). We used the
Cytogenetics Whole-Genome 2.7M platform (Affymetrix) and Chromosome Analysis Suite
program.
Results
Some recurrent aberrations were present in patients from different risk groups and may be
associated with the leukemic process (deletions at 1q42.3, 3q13.2, 3q26.3, 3p14.2, 7q34,
8q12.1, 9p21.3, 12p13.2, 14q11.2, 17q21.3, 22q11.2). Interestingly, we detected new recurrent
aberrations that distinguish the standard risk (7p14.1 and 14q24.2 deletions) and
high risk patients (12q23.1 deletion). We also detected alterations (1q21.3 and 1q25.1 duplication,
5q33.3 alteration, 10q25.1-q25.2 and 12q12 deletion) that distinguish standardrisk
patients who remain in this group from those who were changed to high-risk. These alterations
could be used to improve risk groups classification and treatment individualization.
Conclusions
Risk groups classification could be improved in patients with pediatric B-ALL through the
analysis of new cryptic deletions and duplications.This project was supported by RETICS
(RD/06/0020/0048), Basque Government (GIC10/71, SAI10/03 and 2006111015) and UPV/
EHU (UFI11/35). Support by SGIker (UPV/EHU) is gratefully acknowledged.
20 21

O-06
CCND2 REARRANGEMENTS ARE THE MOST FREQUENT GENETIC EVENTS IN CYCLIN
D1-NEGATIVE MANTLE CELL LYMPHOMA
SALAVERRIA I 1 , ROYO C 1 , NAVARRO A 1 , CAMPO E 1 , BEÀ S 1
1
HOSPITAL CLÍNICO, BARCELONA (RD06/0020/0039)
Cyclin D1-negative mantle cell lymphomas (MCL) are not well characterized, in part due to
the difficulties in their recognition. SOX11 has been recently identified as a reliable biomarker
of MCL, also expressed in the cyclin D1-negative variant. We investigated 40 lymphomas
with MCL morphology and immunophenotype, negative for cyclin D1 expression/t(11;14)
(q13;q32) but SOX11-positive.
These tumors presented clinically with generalized lymphadenopathy, advanced stage, and
had a poor outcome (5-year overall survival 48%). Chromosomal rearrangements of the
CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18/22 cases,
in particular with light chains (10 IGK@, 5 IGL@). No mutations in the phosphorylation
motifs of CCND1, CCND2 and CCND3 were detected.
The global genomic profile and the high complexity of the 32 cyclin D1-negative SOX11-
positive MCL analyzed by copy number arrays were similar to the conventional cyclin D1/
SOX11-positive MCL. 17p deletions and high Ki67 expression conferred a significantly worse
outcome to the patients.
This comprehensive characterization of a large series of cyclin D1-negative MCL indicates
that these tumors are clinically and biologically similar to the conventional cyclin D1-positive
MCL and provides a basis for the proper identification and clinical management of these
patients.
O-07
A DOMINANT-NEGATIVE N-TERMINAL FRAGMENT OF HER2 FREQUENTLY EXPRES-
SED IN BREAST CANCERS
MORANCHO B 1 , PARRA-PALAU JL 1 , IBRAHIM YH 2 , BERNADÓ MORALES C 1 , PEG V 3 , BECH-SERRA
JJ 1 , PANDIELLA A 4 , CANALS F 1 , BASELGA J 2, 5 , RUBIO I 6 , ARRIBAS J 1,7,8
1
PRECLINICAL RESEARCH PROGRAM, VALL D’HEBRÓN INSTITUT D’ONCOLOGIA (VHIO), BARCELONA
(RD06/0020/0022)
2
PRECLINICAL RESEARCH PROGRAM VALL D’HEBRÓN INSTITUT D’ONCOLOGIA (VHIO), BARCELONA
(RD06/0020/0075)
3
PATHOLOGY DEPARTMENT, VALL D’HEBRON UNIVERSITY HOSPITAL AND DEPARTMENT OF MORPHO
LOGICAL SCIENCES, UNIVERSITAT AUTONOMA DE BARCELONA, BARCELONA (RD06/0020/0104)
4
CENTRO DE INVESTIGACIÓN DEL CÁNCER DE SALAMANCA (CIC-IBMCC; USAL-CSIC), SALAMANCA
(RD06/0020/0041)
5
MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER, MASSACHUSETTS GENERAL HOSPITAL, HAR
VARD MEDICAL SCHOOL, BOSTON MA (USA)
6
BREAST SURGICAL ONCOLOGY, BREAST CANCER CENTER, VALL D’HEBRON UNIVERSITY HOSPITAL,
BARCELONA
7
DEPARTMENT OF BIOCHEMISTRY AND MOLECULAR BIOLOGY, UNIVERSITAT AUTONOMA DE BARCELONA,
BARCELONA
8
INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS (ICREA), BARCELONA
The transmembrane tyrosine kinase HER2 (ErbB2, neu) is a prototypical biomarker for
breast cancers and a therapeutic target. Although anti-HER2 therapies are remarkably
effective, HER2-positive tumors are heterogeneous and some subtypes do not respond or
develop resistance to these therapies.
Here we show that H2NTF, a novel Nterminalfragment of HER2, is expressed at variable
levels in 60% of the breast cancer samples analyzed.
Despite this high frequency, none of the cell lines analyzed express the fragment at detectable
levels, while HER2-derived patient-derived xenografts (PDX)present H2NTF expression.
H2NTF was isolated and the C-termini of the fragment was identified by mass spectrometry,
being located at the kinase domain.
Characterization of H2NTF shows that it is devoid of the tyrosine kinase domain but it readily
interacts with full-length HER2 and other HER receptors. As a consequence, H2NTF acts
as a dominant negative, attenuating the signaling triggered by full-length HER receptors.
Expression of H2NTF results in resistance to the treatment with low concentrations of trastuzumab
in vitro. However, cells expressing H2NTF and non-expressing cells have similar
sensitivity to trastuzumab in vivo, likely because H2NTF/trastuzumab complexes trigger
antibody-dependent cell-mediated cytotoxicity.
22 23

O-08
MITOTIC ARREST DOWN-REGULATES FLIP EXPRESSION AND SENSITIZES TUMOR
CELLS TO THE EXTRINSIC PATHWAY OF APOPTOSIS
SÁNCHEZ-PÉREZ T 1 , MEDEMA RH 2 , LÓPEZ RIVAS A 1
1
CENTRO ANDALUZ DE BIOLOGÍA MOLECULAR Y MEDICINA REGENERATIVA (CABIMER), SEVILLA
(RD06-0020-0068)
2
NETHERLANDS CANCER INSTITUTE, NETHERLANDS
Cell cycle deregulation is a feature of tumor cells. Most of the current therapeutic strategies
are based on the perturbation of the cell cycle, especially during mitosis. “Anti-mitotic
drugs” target different mitotic proteins impeding the proper assembly of the mitotic spindle
which triggers mitotic checkpoint activation, mitotic arrest and eventually cell death.
However, after several hours of mitotic arrest, cells may exit mitosis by “slippage”. This
failure to die during mitotic arrest seems to be the main mechanism of resistance to these
treatments.
We have observed that mitotic arrest-induced by these treatments causes the down-regulation
of the anti-apoptotic protein FLIP and consequently, a sensitization to TRAIL-induced
apoptosis in tumor cell resistant to this ligand. Consequently, the combination of TRAIL with
either of these anti-mitotic drugs is much more effective in killing tumor cells and preventing
the slippage process than either of these treatments alone. Recently, in an attempt to
avoid the process of slippage, targeting mitotic exit has been proposed as a better strategy
to kill tumor cells.
Our results demonstrate that FLIP down-regulation induced by mitotic arrest is independent
of checkpoint activation. In this respect, treatments based on combination of mitotic arrestinducing
regimes with TRAIL are much more effective against tumor cells. The mechanism
underlying FLIP down-regulation seems to involve the CDK1/Cyclin B complex but not other
mitotic kinases. Thus, the use of the CDK1 specific inhibitor RO-3306 demonstrates that
FLIP levels inversely correlate with CDK1 activity in mitosis. In contrast, the use of a specific
inhibitor of Plk-1 does not block FLIP down-regulation during mitotic arrest.
Collectively, our results indicate that mitotic arrest sensitizes tumor cells to the extrinsic
pathway of apoptosis by down-regulating FLIP expression and highlight the potential therapeutic
benefit of the combination of mitotic exit-inhibiting treatments and TRAIL against
tumor cells.
O-09
MICRORNA-BASED THERAPY FOR HIGH-RISK NEUROBLASTOMA
SORIANO A 1 , JUBIERRE L 1 , ROMA J 1 , REVENTÓS J 2 , GALLEGO S 1 , SEGURA MF 1 , SÁNCHEZ DE
TOLEDO J 1
1
VALL D’HEBRON INSTITUT DE RECERCA (VHIR), BARCELONA (RD06/0020/1021)
2
VALL D’HEBRON INSTITUT DE RECERCA (VHIR), BARCELONA (RD06/0020/0058)
Neuroblastoma (NBL) is a neoplasm of the sympathetic nervous system, and is the most
common solid tumor in infants. Furthermore, it accounts for 8% to 10% of all childhood
cancers and approximately 15% of cancer deaths in children.
Neuroblastomas are very heterogeneous, with prognosis ranging from spontaneous regression
to aggressive clinical course, and often become refractory to all current forms of
treatment. Patients are assigned to three different risk groups. Overall survival for low-risk
patients is excellent. Minimal intervention is required and sometimes only surgery alone
suffices. Intermediate-risk patients generally have good prognosis and are treated with
surgery and standard chemotherapy.
However, high-risk patients have poor prognosis and need intense chemotherapy. Despite
the aggressive treatment, only 30-40% of patients will be cured. Acquired drug resistance is
often characterized by multiple drug resistance (MDR) defined as coinstantaneous existing
resistance to several structurally and functionally different drugs and composed of diverse
cellular factors and signal transduction pathways such as the DNA Damage Response
process. Owing to the multiple different mechanisms that lead to NBL chemoresistance,
targeting single components of a pathway may not suffice to restore chemosensitivity. In
this respect, it is desirable to find molecules that can regulate multiple cellular processes,
thereby overcoming MDR and improving the therapeutic response.
In this project, we intend to use a new type of epigenetic regulators (microRNAs) to target
the oncogenic properties of MDR neuroblastomas and render them vulnerable to the
currently used chemotherapeutic drugs. We have found a substantial number of genes
implicated in the DNA Damage Response deregulated in high-risk NBL.
Bioinformatic analysis revealed that most of them can be potentially regulated by microR-
NAs. Functional analysis in chemoresistant NBL cell lines identified several microRNAs that
regulate proliferation and sensitivity to the chemotherapeutic drug melphalan. These microRNAs
are promising candidates for NBL therapy.
24 25

O-10
INFLUENCE OF LKB1/STK11 IN GENE EXPRESSION PATTERNS INDUCED BY ENER-
GY STRESS IN LUNG CANCER CELL LINES
GONÇALVES RESTANI R 1 , RODRÍGUEZ NIETO S 1 , SÁNCHEZ CESPEDES M 1
1
PROGRAMA EPIGENETICA I BIOLOGIA DEL CANCER-PEBC/BELLVITGE BIOMEDICAL RESEARCH INSTI
TUTE-IDIBELL BARCELONA (RD06/0020/0062)
The LKB1 gene, also known as STK11 is frequently mutated or deleted in several types of
cancer. Recently, it has been shown that one third of adenocarcinomas carry LKB1 somatic
mutations.
One of the key downstream kinases of LKB1 is the AMP-activated protein kinase (AMPK),
a serine/threonine kinase that serves as a master regulator of energy metabolism. In this
work, we show that upon induced energy stress either by glucose depletion or using AICAR
(5-aminoimidazole-4-carboxamide-1-β-d-riboruranoside), the presence of functional LKB1
is required to regulate the expression of different genes, including the zinc finger transcriptional
activator KLF15 which is involved in regulating gene expression during growth,
differentiation, adipogenesis and gluconeogenesis.
We observed that only those lung cancer cell lines expressing wild type LKB1 are able regulate
the expression of KLF15 under energetic stress, while mutant cell lines do not have
this capability.
Further, we performed either down-regulation or ectopic expression of LKB1 in wild type or
mutant cell lines, respectively, and confirmed these observations.
In addition, upon energy stress conditions, only in LKB1 wild-type cell lines were able to
restore the LKB1/AMPK pathway as evidenced by the phosphorylation of acetyl-CoA carboxylase
(ACC), a target of AMPK. These observations were confirmed after ectopically
restituting LKB1 in mutant cell lines.
Finally, ectopic expression of a dominant negative form of AMPK’s catalytic subunit (alpha-
K95R) prevented the up-regulation KLF15, demonstrating that the pathway requires a
functional AMPK to control the levels of expression of KLF15. Altogether, these results show
the relationship between LKB1, energy metabolism and KLF15.
O-11
IDENTIFICATION OF DIFFERENTIAL GENOMIC AND PROTEOMIC PROFILES ASSO-
CIATED WITH BONE METASTASES IN PROSTATE CANCER
GARCÍA M 1 , RIGAU M 1 , GOMIS R 2 , MOROTE J 3 , REVENTÓS J 1 , DOLL A 1
1
RESEARCH INSTITUTE VALL HEBRON UNIVERSITY BARCELONA (RD06/0020/0058)
2
INSTITUTE FOR RESEARCH IN BIOMEDICINE, BARCELONA
3
VALL HEBRON HOSPITAL, BARCELONA (RD06/0020/0058)
Bone metastases are a frequent and devastating complication in cancer patients, occurring
predominantly in patients with prostate or breast cancer, but also in lung, thyroid, kidney,
and stomach cancer patients. Prostate cancer (PCa) is the most common diagnosed cancer
in men in western world, and skeletal metastases occur in as many as 90% of patients with
advanced PCa. Bone metastatic disease, usually incurable, also has serious clinical manifestations
like severe pain, pathologic fractures, hypercalcemia and spinal cord compression,
making this devastating cancer complication an important and costly health issue.
Objective: To identify novel molecules responsible for the bone metastatic PCa process at
the miRNA, gene and protein level.
Methodology: We serially performed intracardiacal injections (i.c.) of human PCa (PC-3)
stably luciferase expressing cells in male nude mice in order to select a highly bone metastatic
PCa cell population. Cells from bone metastasis were isolated, expanded in culture
and re-injected again into another group of mice. We repeated this step three times. We
used the IVIS System to monitor tumor growth and detect metastases in the living animal.
Genomic and proteomic approaches were done comparing the highly bone metastatic PCa
cell population to the parental one.
Results: The highly bone metastatic PCa cell population obtained by in vivo selection
showed an increased bone metastasis pattern when they were injected in vivo.
Differential genomic profiles of specific miRNAs, genes and proteins with a FC>2 and p-
value

O-12
DIOXIN RECEPTOR CONTROLS CSK-BINDING PROTEIN SIGNALING TO CAVEOLIN 1
AND Β1 INTEGRIN TO MODULATE CELL ADHESION AND MIGRATION
REY-BARROSO J 1 , COLÓ GP 2 , ÁLVAREZ-BARRIENTOS A 1 , REDONDO-MUÑOZ J 2 , CARVAJAL-GONZÁ-
LEZ JM 3 , MULERO-NAVARRO S 3 , GARCÍA-PARDO A 2 , TEIXIDÓ J 2 ,FERNÁNDEZ-SALGUERO PM 1
1
UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
2
CENTRO DE INVESTIGACIONES BIOLÓGICAS (CIB), MADRID (RD06/0020/0011)
3
MOUNT SINAI SCHOOL OF MEDICINE
O-13
CD44 POSITIVITY CONFERS RESISTANCE TO SORAFENIB-INDUCED CELL DEATH IN
HEPATOCELLULAR CARCINOMA (HCC) CELLS
FERNANDO J 1 , ÁLVAREZ-BARRIENTOS A 2 , FERNÁNDEZ-SALGUERO PM 2 , CEPEDA EB 1 , FERNÁNDEZ-
RODRIGUEZ CM 3 , SANCHO P 1 , FABREGAT I 1
1
IDIBELL, BARCELONA (RD06/0020/0097)
2
UNIVERSIDAD DE EXTREMADURA BADAJOZ (RD06/0020/1016)
3
HOSPITAL UNIVERSITARIO FUNDACIÓN ALCORCÓN, MADRID
Recent studies strongly support a regulatory role for the dioxin receptor (AhR) in cell adhesion
and migration.
Following our previous work, we report here that the C-terminal Src kinase-binding protein
(Cbp)-Csk-Src pathway sustains migration of transformed fibroblasts (T-FGM) and regulates
β1 integrin activation andcaveolin-1 (Cav1) tyrosine phosphorylation, and that such
mechanism is AhR dependent. T-FGM AhR-/-fibroblasts had higher integrin β1 activation
that coincided with higher Cbp expression, increased fibronectin secretion and impaired
directional migration.
Notably, interfering Cbp/Pag1 expression in AhR-/- fibroblasts rescued β1 integrin activation,
migration and cell morphology. c-Src activation (Tyr 416) was inhibited, probably
because the increase in Cbp/Pag1 levels produced an accumulation of inhibitory Csk- Cbp/
Pag1 complexes. Consistently, focal adhesion kinase (FAK) phosphorylation was reduced at
Tyr 576 –Tyr 577.
The c-Src target Cav1was hypophosphorylated at Tyr 14, and its association to c-Src diminished
in AhR-/- cells. Interestingly, AhR was present at the plasma membrane in detergent
resistant microdomains (DRM; rafts) and co-immunoprecipitated with Cav1 under basal cell
conditions, revealing a functional link by which AhR could alter Cav1 distribution between
DRM and non-DRM domains.
Furthermore, AhR interference impaired directional migration and Cav1distribution. Thus,
fibroblasts migration requires AhR for proper regulation of the Cbp/Pag1-dependent signaling
to β1 integrin and Cav1.
As Hepatocellular carcinoma (HCC) is the fifth cause of cancer-associated mortality in the
West and one of the leading worldwide causes of death, exists an urge to develop efficacious
tumor-targeted agents [1-4]. Existence of Cancer Stem Cells (CSCs) or Tumor Initiating
Cells (TICs) was proposed forty years ago, but they have only been identified recently
in liver cancers. These cells show a highly-efficient self renewal, ability to differentiate into
different lineages, drug-resistance and tumor regenerating capacity [5]. Their presence
might change therapeutic targeting, since effective approaches could overlook TICs elimination.
In this work we have examined the expression of TIC markers, such as EpCAM,
CD44 or CD90, in different HCC cell lines to establish correlations, if they exist, with the
responsiveness to the first line targeted therapeutic actual option for HCC, i.e., the multikinase
inhibitor sorafenib [6].
Analysis of TICs-related markers allowed us to identify a group of different HCC cell lines
that were EpCAM+/CD44- and another one that were EpCAM-/CD44+. Expression of CD44
correlated with a more de-differentiated and invasive phenotype . Interestingly, CD44+
cells were much less responsive to sorafenib in terms of cell death. Targeting knock-down
of CD44 with specific siRNA sensitized cells to this drug, indicating the direct role played by
CD44 in conferring sorafenib resistance. These results open the possibility for a better fitness
prediction to sorafenib treatment and suggest a potential targeting of CD44 combined
with the use of sorafenib as a strategy on CD44-positive patients. Furthermore, we found
that sorafenib could be interfering in TIC markers presentation, as the inhibitor decreased
the percentage of CD90+ cells, but simultaneously increased EpCAM expression in those
cells that previously expressed it. Future experiments will reveal the relevance of these
effects.
References:
1. Andrisani, O.M., L. Studach, and P. Merle. Semin Cancer Biol. 21(1): p. 4-9.
2. Worns, M.A. and P.R. Galle. Expert Opin Investig Drugs. 19(5): p. 615-29.
3. Luo, J.H., et al. Hepatology. 44(4): p. 1012-24.
4. Villanueva, A., et al. Annu Rev Med. 61: p. 317-28.
5. Rountree, C.B., L. Mishra, and H. Willenbring. Hepatology. 55(1): p. 298-306.
6. Llovet, J.M., et al. N Engl J Med. 359(4): p. 378-90.
We acknowledge Ministerio de Economía y Competitividad, Spain, AGAUR-Generalitat de
Catalunya and IDIBELL for providing research funds and also the Red Temática de Investigación
Cooperativa en Cáncer, RTICC-ISCIII, for funding a mobility program that made this
work possible. We are also deeply grateful to Bayer Schering Pharma AG (Berlin,Germany)
for providing sorafenib.
28 29

O-14
ANALYSIS OF NEW GENES DIRECTLY REGULATED BY FOXE1 IN THYROID CELLS
FERNÁNDEZ LP 1 , SANTISTEBAN P 1
1
INSTITUTO DE INVESTIGACIONES BIOMÉDICAS “ALBERTO SOLS”, MADRID (RD06/0020/0060)
Variations on FOXE1 gene have been extensively associated with several types of cancer
susceptibility, including papillary thyroid cancer. FOXE1 was identified as a thyroid-specific
transcription factor that has a pioneer role during thyroid development and differentiation,
due to its intrinsic capacity to initiate chromatin-opening events. Its function, is essential
for thyroid gland development, as well as for the maintenance of the thyroid differentiated
state in adults. It is known that FOXE1 recognizes and binds to a DNA sequence present in
thyroglobulin (Tg) and thyroperoxidase (Tpo) promoters, two thyroid differentiation genes.
However, FOXE1 binding to other DNA sequences different than Tg and Tpo promoters
remains almost unexplored.
In order to investigate FOXE1 downstream targets in thyroid cells, we performed a genome-wide
screening that provided us insights into FOXE1 transcriptional networks in differentiated
thyroid cells. For this purpose, we used PCCl3 cells, a continuous line of rat
differentiated thyroid follicular cells and we performed whole genome microarray analysis
after knocking-down FOXE1. Microarray data analysis, allowed us to obtain 55 differentially
regulated genes (17 of them were up-regulated and 38 were down-regulated).
O-15
MOLECULAR SUBSETS OF MANTLE CELL LYMPHOMA DEFINED BY THE IGHV MUTATIONAL STA-
TUS AND SOX11 EXPRESSION HAVE DISTINCT BIOLOGICAL AND CLINICAL FEATURES
NAVARRO A 1 , CLOT G 1 , ROYO C 1 , JARES P 1 , HADZIDIMITRIOU A 2 , AGATHANGELIDIS A 2 , BIKOS V 2 ,
DARZENTAS N 2 , PAPADAKI T 2 , SALAVERRIA I 3 , PINYOL M 1 , PUIG X 4 , PALOMERO J 1 , VEGLIANTE MC 1 ,
AMADOR V 1 , MARTÍNEZ A 1 , STEFANCIKOVA L 5 , WIESTNER A 6 , WILSON W 6 , POTT C 7 , CALASANZ
MJ 8 , TRIM N 9 , ERBER W 10 , SANDER B 11 , OTT G 12 , ROSENWALD A 13 , COLOMER D 14 , GINÉ E 15 ,
SIEBERT R 16 , LÓPEZ-GUILLERMO A 15 , STAMATOPOULOS K 2 , BEÀ S 1 , CAMPO E 1
1
PATHOLOGY AND HEMATOLOGY DEPARTMENTS, HOSPITAL CLÍNIC, UNIVERSITY OF BARCELONA, INSTITUTE OF BIOMEDICAL
RESEARCH AUGUST PI I SUNYER (IDIBAPS), BARCELONA (RD06/0020/0039)
2
INSTITUTE OF AGROBIOTECHNOLOGY, CENTER FOR RESEARCH AND TECHNOLOGY HELLAS, THESSALONIKI, GREECE
3
INSTITUTE OF BIOMEDICAL RESEARCH AUGUST PI I SUNYER (IDIBAPS), BARCELONA (RD06/0020/0039)
4
DEPARTMENT OF STATISTICS, TECHNICAL UNIVERSITY OF CATALONIA, BARCELONA
5
DEPARTMENT OF EXPERIMENTAL BIOLOGY, FACULTY OF SCIENCES, MASARYK UNIVERSITY, BRNO, CZECH REPUBLIC
6
HEMATHOLOGY BRANCH, NATIONAL HEART, LUNG, AND BLOOD INSTITUTE, BETHESDA, MD, USA
7
DEPARTMENT OF MEDICINE, UNIVERSITY MEDICAL CENTER SCHLESWIG-HOLSTEIN, KIEL, GERMANY
8
DEPARTMENT OF GENETICS, UNIVERSITY OF NAVARRA, PAMPLONA, (RD06/0020/0078)
9
ADDENBROOKE’S HOSPITAL, CAMBRIDGE, UK
10
SCHOOL OF PATHOLOGY AND LABORATORY MEDICINE, THE UNIVERSITY OF WESTERN AUSTRALIA, NEDLANDS, AUSTRALIA
11
DEPARTMENT OF LABORATORY MEDICINE, KAROLINSKA INSTITUTET, STOCKHOLM, SWEDEN
12
DEPARTMENT OF CLINICAL PATHOLOGY, ROBERT-BOSCH-KRANKENHAUS AND DR.MARGARETE FISCHER-BOSCH
INSTITUTE OF CLINICAL PHARMACOLOGY, STUTTGART, GERMANY
13
UNIVERSITY OF WÜRZBURG, WÜRZBURG, GERMANY
With the aim of investigating new FOXE1 direct targets, we searched for a specific FOXE1
binding sequence in promoter regions of FOXE1 statistically significant regulated genes
(+/-1000pb). FOXE1 binding sequence was presented in promoter regions of 26 out of
55 differentially FOXE1 deregulated genes. In five of these promoter sequences, we have
performed chromatin inmunoprecipitation analysis (ChIP).
From this study we conclude that in vivo, FOXE1 binds to three regulatory regions, located
close to two genes involved in thyroid differentiation and consequently, in transformation.
They are new direct downstream targets of FOXE1. Furthermore, this study point out the
important role of FOXE1 in regulation of a large number of genes in thyroid cells, which
need to be evaluated by further studies.
14
PATHOLOGY AND HEMATOLOGY DEPARTMENTS, HOSPITAL CLÍNIC, UNIVERSITY OF BARCELONA, INSTITUTE OF
BIOMEDICAL RESEARCH AUGUST PI I SUNYER (IDIBAPS), BARCELONA (RD06/0020/0014)
15
PATHOLOGY AND HEMATOLOGY DEPARTMENTS, HOSPITAL CLÍNIC, UNIVERSITY OF BARCELONA, INSTITUTE OF
BIOMEDICAL RESEARCH AUGUST PI I SUNYER (IDIBAPS), BARCELONA (RD06/0020/0051)
16
INSTITUTE OF HUMAN GENETICS, UNIVERSITY KIEL, KIEL, GERMANY
Mantle cell lymphoma (MCL) is a heterogeneous disease with most patients following an aggressive
clinical course while others have an indolent behavior. We performed an integrative and
multidisciplinary analysis of 177 MCL to determine whether the immunogenetic features of the
clonotypic B cell receptors may identify different subsets of tumors. ‘Truly unmutated’ (100%
identity) IGHV genes were found in 24% cases, 40% were ‘minimally/borderline mutated’ (99.9-
97%), 19% ‘significantly mutated’ (96.9-95%) and 17% ‘hypermutated’ (

O-16
ETV5 AND FOXM1 TRANSCRIPTION FACTORS ARE OVEREXPRESSED IN
OVARIAN CANCER AND REGULATE CELLULAR ADHESION AND PROLIFE-
RATION CONTRIBUTING TO TUMOR DISSEMINATION
LLAURADÓ M 1 , MAJEM B 2 , CASTELLVÍ J 2 , CABRERA S 3 , PÉREZ-BENAVENTE A 3 , COLÁS E 1 , RIGAU
M 1 , OLIVÁN M 1 , DOLL A 1 , ABAL M 1 , DOLCET X 4 , MATÍAS-GUIU X 4 , GIL-MORENO A 3 , XERCAVINS
J 3 , RUIZ A 1 , REVENTÓS J 1
O-17
COUNTERACTING AUTOPHAGY OVERCOMES RESISTANCE TO EVEROLI-
MUS IN MANTLE CELL LYMPHOMA
ROSICH L 1 , XARGAY-TORRENT S 1 , G. LÓPEZ-GUERRA M 1 , CAMPO E 2 , COLOMER D 1 , ROUE G 1
1
HOSPITAL CLÍNIC–IDIBAPS, BARCELONA (RD06/0020/0014)
2
HOSPITAL CLÍNIC–IDIBAPS, BARCELONA (RD06/0020/0039)
1
INSTITUT RECERCA VALL HEBRÓN, BARCELONA (RD06/0020/0058)
2
PATOLOGÍA HOSPITAL VALL HEBRÓN, BARCELONA (RD06/0020/0058)
3
GINECOLOGÍA HOSPITAL VALL HEBRÓN BARCELONA (RD06/0020/0058)
4
IRB LLEIDA (RD06/0020/1034)
Background and aims: Epithelial ovarian cancer is the most lethal gynecological malignancy
and the fifth leading cause of cancer deaths in women in the Western world. ETS transcription
factors are known to act as positive or negative regulators of the expression of genes that are
involved in various biological processes. We have characterized the upregulation of the ETV5
gene (an ETS transcription factor) in endometrial cancer (Monge M 2005, 2007, 2009; Planagumà
J 2011; Colás E 2012). In the present study we have investigated the role of ETV5 in epithelial
ovarian cancer.
Methods: We analyzed ETV5 expression by quantitative RT-PCR and immunohistochemistry in
ovarian tumor samples and controls. We examined the biological effects of modulating ETV5
expression in two different human ovarian cancer cell lines. We analyzed cell adhesion proteins
by using immunofluorescence and Western blot, and we performed proliferation, migration, adhesion
and apoptosis assays. Moreover, we analyzed by gene expression microarray technology
those genes whose expression was altered in an ovarian cancer cell line with a stable downregulation
of ETV5.
Results: We found ETV5 upregulated in ovarian tumor samples compared to ovarian tissue
controls. The in vitro inhibition of ETV5 decreased cell proliferation in serum-deprived conditions,
induced EMT and decreased cell adhesion to extracellular matrix components. ETV5 inhibition
also decreased cell-cell adhesion and induced apoptosis in anchorage independent conditions.
Accordingly, ETV5 upregulation induced the expression of cell adhesion molecules and enhanced
cell survival in a spheroid model. The analysis of the genes and signaling pathways under the control
of ETV5 in OV90 cells has unraveled new signaling pathways that interact with ETV5, among
them the cell cycle progression and the TGFβ signaling pathway. In addition, we found that the
down-regulation of ETV5 reduced the expression of the oncogenic transcription factor FOXM1.
Consistently, FOXM1 was over-expressed in ovarian tumor samples, and its transcriptional levels
increased with ETV5 transcription in ovarian tumor samples. Moreover, FOXM1 expression levels
increased with tumor grade, suggesting a role in the progression of ovarian cancer.
Conclusions: Our findings suggest that the overexpression of ETV5 detected in ovarian cancer
cells may contribute to ovarian tumor progression through the ability of ETV5 to enhance ovarian
cancer cell proliferation and ovarian cancer cell dissemination and metastasis into the peritoneal
cavity by regulating the expression of cell adhesion molecules as E-cadherin as well as other
transcription factors as FOXM1.
References: Llauradó et al., Int J Cancer 2011; Llauradó et al., Mol Cancer Res 2012.
Mantle cell lymphoma (MCL) is an aggressive B-lymphoid neoplasm with poor response to conventional
chemotherapy and short survival. The phosphatidylinositol 3-kinase/Akt/mTOR survival
pathway is constitutively activated in MCL cells, thereby making the mTOR inhibition an attractive
therapeutic strategy. The first clinical studies of everolimus (RAD001), an mTOR inhibitor, in relapsed
MCL patients have reported a significant response. Our aim was to analyze the mechanism
related to everolimus resistance/sensitivity in MCL cells.
Sensitivity to everolimus was analyzed in MCL cell lines and primary MCL cells. Everolimus mechanism
of action was determined by flow cytometry, and western blot. Particularly, autophagy was
studied by LC3BI/II expression, autophagolysosomes detection by flow cytometry and fluorescence
microscopy, and siRNA-mediated gene silencing.
Everolimus exerted antitumoral effect on MCL cells while sparing normal cells. In MCL cell lines
this phenomenon was associated to G1 cell-cycle arrest, dephosphorylation of the mTOR downstream
targets, 4E-BP1 and S6RP, and rephosphorylation of Akt. A synergistic cytotoxic effect was
observed between everolimus and an Akt inhibitor, which overcame the compensatory reactivation
within the mTOR signaling pathway. Interestingly, MCL cells with low response to this combination
showed high levels of autophagy. Accordingly, selective triple knockdown of the autophagy
genes ATG7, ATG5 and ATG3, and pre-treatment with the autophagy inhibitor hydroxychloroquine
efficiently overcame the resistance to Akt/mTOR inhibitors, leading to the activation of the mitochondrial
apoptotic pathway.
These results suggest that autophagy induction protects MCL cells from Akt/mTOR targeting
and counteracting autophagy may represent an attractive strategy for sensitizing MCL cells to
everolimus-based therapy.
This work was supported (in part) by grants from Fondo de Investigación Sanitaria (PI09/0060)
(to GR), Ministerio de Ciencia e Innovación (SAF 09/9503) (to DC), Red Temática de Investigación
Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of
Economy and Competitiveness (RED 2006-20-014 to DC and 2006-20-039 to EC) and Generalitat
de Catalunya (2009SGR967 to DC). LR and SX-T are recipients of predoctoral fellowships from
IDIBAPS and Ministerio Ciencia e Innovación (FPU), respectively. ML-G has a contract from RED
2006-20-014.
32 33

O-18
PIK3CA ALTERATIONS IN BLADDER CANCER RECURRENCE
MARTÍNEZ-FERNÁNDEZ M 1 , DUEÑAS M 1 , GARCÍA ESCUDERO R 1 , VILLACAMPA F 2 , DUARTE J 2 ,
MARTÍNEZ V 2 , GÓMEZ MJ 2 , MARTÍN ML 2 , FERNÁNDEZ M 2 , CASTELLANO D 2 , RODRÍGUEZ-PERALTO
JL 2 , DE LA ROSA F 2 , PARAMIO J 1
1
CENTRO DE INVESTIGACIONES ENERGÉTICAS, MEDIOAMBIENTALES Y TECNOLÓGICAS (CIEMAT),
MADRID (RD06/0020/0029)
2
HOSPITAL 12 DE OCTUBRE, MADRID
The phosphatidylinositol 3 kinase (PI3K) pathway is one of the major pathways modulating
cell growth, proliferation, metabolism, survival, and angiogenesis. Interestingly, hyperactivation
of this pathway is one of the most frequent occurrences in human cancer and is thus
an obvious target for treatment of this disease.
Here, we study its role in bladder cancer, the fifth most common cancer in the world. It is
a complex disease caused by both genetic and environmental factors, and constitutes an
important problem for health care systems due to its frequent recurrences, being one of
the most costly malignancies.
We have analyzed the mutation, copy gain and expression of PIK3CA gene, which encodes
the p110α catalytic subunit of PI3K, in a series of human bladder cancer samples and their
corresponding healthy mucosas. Our data indicate a high frequency of alterations in this
gene that seems to determine a reduced likelihood of recidive. Gene expression studies
indicated that increased recurrence probability is associated reduced expression of genes,
mediated by polycomb repressive complex, which showed increased expression in tumors
bearing PIK3CA gene alterations. Therefore, our data support that PIK3CA status may constitute
a good prognostic factor in recurrence of bladder cancer and revealed a previously
non reported inverse correlation between PIK3CA gene alteration and polycomb repressive
complex function that might help to identify new therapeutic avenues for bladder cancer
patients.
O-19
PAPEL DEL CORREPRESOR NcoR EN LA INHIBICIÓN DE LA INVASIVIDAD
Y FORMACIÓN DE METÁSTASIS POR TRβ
MARTÍNEZ IGLESIAS O 1 , MARTÍN OROZCO R 1 , ARANDA IRIARTE A 1
1
INSTITUTO DE INVESTIGACIONES BIOMÉDICAS “ALBERTO SOLS”, MADRID (RD06/0020/0036)
Los receptores de hormonas tiroideas (TRs) desempeñan un papel fundamental en procesos
de proliferación y homeostasis y se expresan ubicuamente en los tejidos normales. Sin
embargo, en células tumorales esta expresión se encuentra reducida y se han detectado
alteraciones y mutaciones.
Resultados previos de nuestro laboratorio han descrito que la expresión de TRβ inhibe
la tumorigénesis, invasividad y formación de metastasis, al menos en parte, mediante la
inhibición de la expresión de una amplia variedad de genes prometastásicos como COX2,
MMP9 e ID1.
Varios mecanismos podrían explicar este efecto supresor tumoral y metastásico del TRβ.
En este trabajo analizamos la posibilidad de que la inhibición de genes prometastasicos,
invasividad y metastasis sea debida al reclutamiento de complejos correpresores.
Hemos observado que la expresión del correpresor NcoR se encuentra aumentada tanto en
la línea celular de hepatocarcinoma sk-hep1 que expresa TRβ (SK-TRβ) como en los tumores
formados por estas células en ratones inmunosuprimidos. Además, el silenciamiento de
NcoR mediante técnicas de RNA de interferencia produce un claro aumento en los niveles
de expresión de los genes prometastásicos COX2, MMP9 e ID1. Este silenciamiento también
produce un aumento en la invasividad en ensayos in vitro a través de matrigel y aumenta
la extravasación de las células tumorales en pulmón cuando son inoculadas en la vena de
la cola de ratones inmunosuprimidos.
Por otro lado, la represión de la expresión génica por los TRs puede deberse a una union
directa a HRE negativos o a mecanismos de cross-talk con otras vías de señalización. Mediante
transfecciones transitorias hemos localizado sitios CRE, AP1 y SP1 en los promotores
de los genes prometastásicos que parecen responsables del efecto inhibitorio del TRβ.
Todos estos datos corroboran el papel del correpresor NcoR en la inhibición de genes prometastasicos,
invasividad y extravasación por parte de TRβ.
34 35

O-20
DIFFERENTIAL FUNCTIONS OF EVI1 SPLICE ISOFORMS IN CELL VIABI-
LITY AND TRANSCRIPTIONAL REGULATION. THE EVI1 HUMAN PROTEIN
REGULATES ITS OWN TRANSCRIPTION
MAICAS M 1 , VÁZQUEZ I 1 , VICENTE C 1 , MARCOTEGUI N 1 , URQUIZA L 1 , CALASANZ MJ 1 , ODERO
MD 1
1
CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA), PAMPLONA (RD06/0020/0078)
Overexpression of EVI1 (3q26) leads to aggressive forms of human acute myeloid leukemia
(AML). Numerous studies have addressed the biological functions of this protein; however,
the mechanism by which EVI1 operates in the transformation of hematopoietic cells remains
unclear. The MDS1 and EVI1 complex locus (MECOM) codes for at least 4 different
proteins: EVI1-145kDa, EVI1-RP-9, Δ324, and MDS1EVI1.
Our aim was to study these still uncharacterized isoforms, in order to better understand the
biological activities of EVI1 in AML.
Analysis at mRNA and protein level of cell lines and AML patient samples showed diverse
expression patterns of these isoforms, and functional experiments showed that EVI1-
145kDa and EVI1-RP-9 increased cell viability by reducing the number of apoptotic cells,
and MDS1EVI1 induced cell apoptosis. Moreover, bioinformatic analysis, ChIP assays and
luciferase experiments showed that the EVI1 transcription factor acts as a regulator of its
own expression: the EVI1-RP-9, Δ324 and MDS1EVI1 isoforms repress its transcription,
while EVI1-145kDa acts as an activator. Finally, we found that EVI1-145kDa, EVI1-RP-9,
and Δ324 activate the transcription of GATA2, a well-known target of EVI1, while MDS1EVI1
represses it.
Our results support the complex functional role of this protein and open new directions to
further understand the mechanisms of EVI1 overexpressing leukemias
36 37

P-01 “HOMEOBOX NKX2-3 PROTEIN INDUCES ONCOGENIC TRANSFORMATION IN
B-CELL LYMPHOMA”
MARIA MENA VARAS. CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA), PAMPLONA (RD06/0020/0088)
P-02 “THE DIOXIN RECEPTOR SUPPRESSES MELANOMA GROWTH AND METAS-
TASIS BY DIFFERENTIALLY ACTING ON THE TUMOR CELL AND THE MICROENVIRON-
MENT”
MARIA CONTADOR TROCA. UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
P-03 “TETRACHLORODIBENZO-P-DIOXIN DISRUPTS INTRACELLULAR CALCIUM
HOMEOSTASIS IN HUMAN NEURONAL CELL LINE SHSY5Y”
ANTONIO MORALES HERNÁNDEZ. UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
P-04 “CHILDHOOD SOLID TUMOURS SURVIVAL IN SPAIN 1980-2006:TIME TRENDS
AND VARIATIONSBY AGE AND SEX”
SARAY FELIPE GARCÍA. REGISTRO NACIONAL DE TUMORES INFANTILES. UNIVERSITAT DE VALENCIA (RD06/0020/0033)
P-05 “SOX11 REGULATES PAX5 EXPRESSION AND BLOCKS TERMINAL B-CELL DI-
FFERENTIATION IN AGGRESSIVE MANTLE CELL LYMPHOMA”
MARIA CARMELA VEGLIANTE. INSTITUT D’INVESTIGACIONS AUGUST PI I SUNYER – IDIBAPS (RD06/0020/0039)
P-06 “VEGF-R2: ¿NUEVO PREDICTOR DE METÁSTASIS EN CARCINOMA DE MER-
KEL?”
SILVIA CARNICERO CÁCERES. HOSPITAL UNIVERSITARIO MARQUÉS DE VALDECILLA (RD06/0020/0107)
P-07 “DIOXIN RECEPTOR KNOCK-DOWN PROMOTES PRIMARY AND TGF-INDUCED
EPITHELIAL-MESENCHYMAL TRANSITION”
EVA MARÍA RICO LEO. UNIVERSIDAD DE EXTREMADURA, BADAJOZ (R006/0020/1016)
P-08 “ANÁLISIS DE LAS ALTERACIONES CITOGENÉTICAS EN 2131 PACIENTES CON
LLC Y LBM. ESTUDIO MULTICÉNTRICO DEL GCECGH Y GELLC”
ANNA PUIGGROS METJE. HOSPITAL DEL MAR, PARC DE SALUT MAR BARCELONA (RD07/0020/2004)
P-09 “GENETIC ABERRATIONS IN PEDIATRIC FOLLICULAR LYMPHOMA”
IDOA MARTÍN GUERRERO. UNIVERSIDAD DEL PAÍS VASCO, BILBAO (RD06/0020/0048)
P-10 “MOLECULAR PATHWAYS REGULATED BY ETV5 TRANSCRIPTION FACTOR IN
THE INVASION OF ENDOMETRIAL CARCINOMA”
NURIA PEDROLA MONTERO. INSTITUT RECERCA VALL HEBRÓN, BARCELONA (RD06/0020/0058)
P-11 “ANALISIS DE LA EXPRESION DE MKP1 Y MKP3 EN MUESTRAS DE PACIENTES
DE CANCER DE MAMA”
EDUARDO TORMO MARTÍN. FUNDACIÓN INVESTIGACIÓN CLÍNICO VALENCIA / INCLIVA (RD06/0020/0080)
P-13 “ACADESINE EXERTS ANTITUMORAL ACTIVITY AND COOPERATES WITH RI-
TUXIMAB IN IN VITRO AND IN VIVO MODELS OF MANTLE CELL LYMPHOMA”
ARNAU MONTRAVETA SIMON. HOSPITAL CLÍNIC-IDIBAPS, BARCELONA (RD06/0020/0014)
P-14 “AICAR INDUCES BAK/BAK-DEPENDENT APOPTOSIS THROUGH UP-REGULA-
TION OF THE BH3-ONLY PROTEINS BIM AND NOXA IN MOUSE EMBRYO FIBROBLASTS”
CRISTINA MONCUNILL MASSAGUER. INSTITUT D’INVESTIGACIÓ BIOMÈDICA DE BELLVITGE (IDIBELL)–UNIVERSITAT DE
BARCELONA, BARCELONA (RD06/0020/0097)
P-15 “DETERMINATION OF SNAIL1 PARACRINE FUNCTIONS: IMPLICATION IN
PRO-TUMOROGENIC ABILITIES ON COLORECTAL EPITHELIAL CELLS LINES”
ALBERTO HERRERA TEJERO. HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-MAJADAHONDA (RD06/0020/0020)
P-16 “MEAT CONSUMPTION AND OESOPHAGEAL ADENOCARCINOMA RISK IN THE
EPIC COHORT”
LEILA LUJÁN BARROSO. INSTITUT CATALÀ D’ONCOLOGIA/IDIBELL, BARCELONA (RD06/0020/0091)
P-17 “ΔNp73 UPREGULATION CORRELATES WITH POOR PROGNOSIS OF COLON
CANCER PATIENTS”
CORAL SAN MILLÁN BLANCO. HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-UAM, MADRID (RD06/0020/0020)
P-18 “DIFFERENT EXOSOME CARGO FROM PLASMA/BRONCHOALVEOLAR LAVAGE
IN NON-SMALL-CELL LUNG CANCER”
MARTA RODRÍGUEZ MORENO. FUNDACIÓN PARA LA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL UNIVERSITARIO PUERTA DE
HIERRO-MAJADAHONDA MADRID (RD06/0020/0020)
P-19 “GENE EXPRESSION PROFILE ASSOCIATED WITH OVARIAN CANCER DISSE-
MINATION. A COMPARATIVE STUDY OF OVARIAN PRIMARY TUMORS, ASCITES AND
METASTASES”
BLANCA MAJEM CAVALLER. INSTITUT RECERCA VALL HEBRÓN, BARCELONA (RD06/0020/0058)
P-20 “THE POLARITY GENE PARD3 IS INACTIVATED IN SQUAMOUS CELL CARCINO-
MAS OF THE LUNG”
ESTER BONASTRE LLORT. INSTITUT D’INVESTIGACIÓ BIOMÈDICA DE BELLVITGE (IDIBELL), BARCELONA
(RD06/0020/0062)
P-21 “FUNCTIONAL ANALYSIS OF THE GATA2 PROMOTER SHOWS THAT MUTA-
TIONS OF GATA2 IMPAIR ITS OWN TRANSCRIPTIONAL REGULATION”
XABIER CORTÉS LAVAUD. CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA), PAMPLONA (RD06/0020/0078)
P-22 “ÍNDICE DE RIESGO BASADO EN GENES ANGIOGÉNICOS. VALOR PRONÓSTI-
CO EN PACIENTES CON CÁNCER DE PULMÓN NO MICROCÍTICO (CPNM) RESECABLE”
MARTA USÓ MARCO. HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA, VALENCIA (RD06/0020/1024)
P-12 “HETEROGENEITY OF CANCER-ASSOCIATED FIBROBLASTS FROM HUMAN
PRIMARY COLON TUMORS IN THEIR PRO-TUMOROGENIC ABILITIES ON CANCER
CELLS”
P-23 “ETV5 REGULATES IGCAMS SUPERFAMILY DURING MYOMETRIAL INVASION”
LAURA DEVIS JAUREGUI. INSTITUT RECERCA VALL HEBRÓN, BARCELONA (RD06/0020/0058)
MERCEDES HERRERA TORRES. HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-MAJADAHONDA (RD06/0020/0020)
38 39

P-24 “NOX4 PLAYS A TUMOR SUPRESSOR ROLE IN HEPATOCELLULAR CARCINOMA
CELLS”
EVA CROSAS MOLIST. INSTITUT D’INVESTIGACIÓ BIOMÈDICA DE BELLVITGE (IDIBELL), BARCELONA
(RD06/0020/0097)
P-25 “AhR BINDING TO Alu ELEMENTS X14S, X36S AND X45S MODULATES THE
EXPRESSION OF STEMNESS-RELEVANT GENES Oct4, Nanog, Shh AND Sox2”
FRANCISCO JAVIER GONZÁLEZ RICO. UNIVERSIDAD DE EXTREMADURA, BADAJOZ (R006/0020/1016)
P-26 “SECUENCIACIÓN DE ALTO RENDIMIENTO PARA LA CARACTERIZACIÓN
DEL MIRNAOMA EN CPNM EN ESTADIOS INICIALES. ANÁLISIS DE EXPRESIÓN
DIFERENCIAL”
SANDRA GALLACH GARCIA. HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA, VALENCIA (RD06/0020/1024)
P-27 “ISOLATION AND CHARACTERISATION OF RHABDOMYOSARCOMA-INITIA-
TING CELLS”
ANA ALMAZÁN MOGA. INSTITUT DE RECERCA HOSPITAL UNIVERSITARI VALL D’HEBRON, BARCELONA (RD06/0020/1021)
P-28 “EFFECTS OF GAMMA-SECRETASE INHIBITORS IN RHABDOMYOSARCOMA
MOUSE MODELS”
CARLA MOLIST MUÑOZ. INSTITUT DE RECERCA HOSPITAL UNIVERSITARI VALL D’HEBRON, BARCELONA (RD06/0020/1021)
P-29 “MOLECULAR EVENTS IN ENDOMETRIAL CARCINOSARCOMAS AND THE ROLE
OF HMGA2 IN ENDOMETRIAL CARCINOGENESIS”
LAURA ROMERO PÉREZ. INSTITUTO DE BIOMEDICINA DE SEVILLA (IBIS), SEVILLA (RD06/0020/0013)
P-30 “GENETIC VARIANTS IN MIRNAS: NEW PREDICTIVE MARKERS IN THE
ORIGIN OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA”
ANGELA GUTIÉRREZ CAMINO. UNIVERSIDAD DEL PAÍS VASCO, BILBAO (RD06/0020/0048)
P-31 “ACTIVITY OF LENALIDOMIDE IN IN VITRO AND IN VIVO MODELS OF
BORTEZOMIB-RESISTANT MANTLE CELL LYMPHOMA”
ALEXANDRA MOROS SANZ. HOSPITAL CLÍNIC-IDIBAPS (RD06/0020/0014)
P-32 “VALOR PRONÓSTICO DE LA EXPRESIÓN DEL RECEPTOR CANNABINOIDE
TIPO 2, CB2, EN CÁNCER COLORRECTAL HUMANO”
ESTHER MARTÍNEZ MARTÍNEZ. HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-MAJADAHONDA, MADRID
(RD06/0020/0020)
P-33 “MNT, EL PRIMO GRANDE DE LA RED MYC”
Mª CARMEN LAFITA NAVARRO. INSTITUTO DE BIOMEDICINA Y BIOTECNOLOGÍA DE CANTABRIA (IBBTEC), SANTANDER
(RD06/0020/0017)
P-34 “CARACTERIZACIÓN CLÍNICA Y BIOLÓGICA DEL LINFOMA DE LA ZONA
MARGINAL ESPLÉNICO CON Y SIN LINFOCITOS VELLOSOS CIRCULANTES”
ANNA CALULL BAGÓ. HOSPITAL DEL MAR, PARC DE SALUT MAR BARCELONA (RD07/0020/2004)
P-35 “ROLE OF AhR IN MURINE SPERMATOGENESIS THROUGH REGULATION OF
THE SINE B1-X35S RETROTRANSPOSON”
40 41
NURIA MORENO MARÍN. UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
P-36 “DIETARY IRON, HEME IRON AND BODY IRON STATUS AND CANCER RISK – A
SYSTEMATIC REVIEW”
ANA CELESTE FONSECA NUNES. INSTITUTO CATALÁN DE ONCOLOGÍA (ICO)-IDIBELL, BARCELONA (RD06/0020/0091)
P-37 “IDENTIFICATION OF PROTEIN BIOMARKERS TO IMPROVE EARLY DIAGNO-
SIS IN ENDOMETRIAL CANCER”
ELENA MARTÍNEZ GARCÍA. HOSPITAL VALL D´HEBRÓN, BARCELONA (RD06/0020/0058)
P-38 “URINE EXOSOME-DERIVED BIOMARKERS FOR THE EARLY DETECTION OF
PROSTATE CANCER”
TAMARA SEQUEIROS FONTÁN. INSTITUT RECERCA VALL HEBRÓN (VHIR), BARCELONA (RD06/0020/0058)
P-39 “NOVEL IDENTIFICATION OF EXOSOMES IN UTERINE ASPIRATES AND ITS
UTILITY AS A SOURCE FOR NEW BIOMARKERS”
IRENE CAMPOY MONCAYO. HOSPITAL VALL D´HEBRÓN, BARCELONA (RD06/0020/0058)
P-40 “INHIBITORY MECHANISMS OF THE RESPONSE TO TGF-B BY THE THYROID
HORMONE RECEPTORS”
ELVIRA ALONSO MERINO. INSTITUTO DE INVESTIGACIONES BIOMÉDICAS “ALBERTO SOLS”, MADRID (RD06/0020/0036)
P-41 “LA FOSFORILACIÓN DE eIF4E AUMENTA LA SUPERVIVENCIA Y EL CRECI-
MIENTO CELULAR BAJO SITUACIONES DE ESTRÉS”
ALBA MARTÍNEZ DÍAZ. INSTITUT RECERCA VALL HEBRÓN (VHIR), BARCELONA (RD06/0020/0104)
P-42 “EXPRESIÓN DE GENES INMUNOREGULADORES EN CÁNCER DE PULMÓN NO
MICROCÍTICO”
ADRIÁN ALMAGRO LARROSA. HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA, VALENCIA (RD06/0020/1024)
P-43 “ESTUDIO DE CAMBIOS FOCALES EN EL NÚMERO DE COPIAS DE DNA EN
NEUROBLASTOMA MEDIANTE ARRAYS DE SNP”
ANA PILAR BERBEGALL BELTRÁN. FACULTAD DE MEDICINA –UNIVERSIDAD DE VALENCIA, VALENCIA (RD06/0020/0102)
P-44 “MicroRNAs IN URINE AS BIOMARKERS FOR PROSTATE CANCER”
MELÀNIA MONTES PÉREZ. INSTITUT RECERCA VALL HEBRÓN (VHIR), BARCELONA (RD06/0020/0058)
P-45 “METHODS FOR RNA AND miRNA PURIFICATION IN EXOSOMES FROM URINE
OF PROSTATE CANCER PATIENTS”
MIREIA OLIVAN RIERA. INSTITUT RECERCA VALL HEBRÓN (VHIR), BARCELONA (RD06/0020/0058)
P-46 “P95HER2/90-100kDa INDUCED SIGNALING LEADS TO APOPTOSIS ELUCIDA-
TING A POSSIBLE MOLECULAR SWITCH BETWEEN OIS AND APOPTOSIS”
CRISTINA BERNADÓ MORALES. VALL D’HEBRÓN INSTITUT D’ONCOLOGIA (VHIO), BARCELONA (RD06/0020/0022)
P-47 “ACTIVATION OF THE CLASSICAL COMPLEMENT PATHWAY IN LUNG CANCER:
A NOVEL BIOMARKER FOR DIAGNOSIS AND PROGNOSIS”
DANIEL AJONA MARTÍNEZ-POLO. CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA), PAMPLONA
(RD06/0020/0066)

,
43

P-01
HOMEOBOX NKX2-3 PROTEIN INDUCES ONCOGENIC TRANSFORMATION
IN B-CELL LYMPHOMA
MENA M 1 , ROBLES EF 1 , ALDAZ B 1 , AKASAKA T 2, MACRI-PELLIZZERI L 3
1
CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA), PAMPLONA (RD06/0020/0088)
2
UNIVERSITY OF LEICESTER
3
CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA), PAMPLONA (RD06/0020/0111)
Molecular cloning of chromosomal translocation t(10;14)(q24;q32) in B-cell lymphoma cells
identified NKX2.3, a gene encoding a homeobox transcription factor, fused to IGH, which
resulted in an increase of gene expression with respect normal lymphocytes. In addition,
NKX2-3 over-expression was detected in 49 of 170 (29%) patients with splenic and extranodal
marginal-zone (MZ) lymphomas and diffuse large B-cell lymphoma (DLBCL) but not
in other mature B-cell malignancies. To determine the potential oncogenic role of NKX2-3,
transgenic mice with restricted expression of human NKX2-3 to lymphocytes were generated.
Young mice developed partial bone marrow (BM) blockade in the pre-B1-to-pre-B2
transition accompanied by a decrease in the number of circulating B lymphocytes. From
~12 months of age, mice started to develop clinical signs of disease and were euthanized,
showing massive splenomegaly (5-10 times larger than normal controls) in all cases
(n=46). Immunohistochemical studies showed that the infiltrating cells were mature B
lymphocytes, with reactive CD3+ T lymphocytes. In 55% of the mice, additional extranodal
tumors involving the lungs, liver and kidneys were detected, showing infiltrates of small
mature B lymphocytes. Using gene expression microarray analysis, a significant overlap
was found between transcriptional signatures of the mouse NKX2-3 splenic lymphomas
and human SMZLs, including genes known to be involved in human SMZL pathogenesis.
Moreover, these tumors showed activation of JNK and JAK-STAT3 pathways, and non-canonical
NF-kB signaling. Taken together, these data indicate that the murine tumors closely
resembled human splenic and extranodal marginal-zone (MALT) lymphomas. Furthermore,
analysis of splenic and extranodal lymphomas from mice older than 18 months revealed
areas of high-grade transformation to DLBCL, further highlighting the parallelism between
splenic and human lymphomas. In conclusion, NKX2-3 protein is over-expressed in a subset
of patients with SMZL, MALT lymphoma and DLBCL, and that the ectopic expression of
NKX2-3 in mouse B lymphocytes recapitulates the main features of the human lymphoma
counterparts.
P-02
THE DIOXIN RECEPTOR SUPPRESSES MELANOMA GROWTH AND METAS-
TASIS BY DIFFERENTIALLY ACTING ON THE TUMOR CELL AND THE MI-
CROENVIRONMENT
CONTADOR M 1 , ÁLVAREZ A 1 , BARRASA E 1 , RICO EM 1 , CATALINA FERNÁNDEZ I 2 , MENACHO M 3 ,
BUSTELO XR 3 , GÓMEZ DURÁN A 2 , SAEZ-SANTAMARÍA J 2 ,FERNÁNDEZ-SALGUERO P 1
1
UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
2
HOSPITAL INFANTA CRISTINA
3
CENTRO DE INVESTIGACIÓN DEL CÁNCER DE SALAMANCA (CIC-IBMCC; USAL-CSIC),
SALAMANCA (RD06/0020/0001)
Metastatic melanoma is steadily rising in the population with poor rate of patient survival.
Finding prognostic and therapeutic targets for melanoma is therefore a major issue in
cancer. The dioxin receptor (AhR) has a role in cell proliferation and migration. Yet, our
knowledge of how AhR affects tumor growth and dissemination remains largely limited.
Here we report that AhR suppresses melanoma growth and metastasis in vivo. As a consequence,
B16F10 cells lacking AhR expression (sh-AhR) displayed exacerbated melanoma
primary tumorigenesis and lung metastasis when introduced in the stroma of wild type
recipient mice. By contrast, sh-AhR B16F10 cells failed to enhance melanoma progression
and metastasis when introduced in AhR-/- mice. Thus, AhR knock-down in the melanoma
cell requires stromal AhR expression to reach maximum tumor progression and metastasis.
Consistently, constitutive activation of AhR in B16F10 cells suppressed melanoma progression
regardless of stromal AhR.
The intrinsic tumor suppressor-like functions of AhR in melanoma cells are connected to
its role in the blockage of stem cell populations and of molecular intermediates of the promotility
(1 integrins) and anti-motility (caveolin1) machinery. Consistent with this tumor
inhibitory role of AhR, we observed that AhR expression is reduced in human melanoma
tumors versus nevi lesions. Moreover, the pattern of AhR down-modulation in malignant
melanoma concurs with that of the putative tumor suppressor caveolin1.
Therefore, AhR could serve as a molecular marker in melanoma and its activation in the
tumor and stromal compartments should be taken into consideration.
44 45

P-03
TETRACHLORODIBENZO-P-DIOXIN DISRUPTS INTRACELLULAR
CALCIUM HOMEOSTASIS IN HUMAN NEURONAL CELL LINE SHSY5Y
MORALES-HERNÁNDEZ A 1 , SÁNCHEZ-MARTÍN F J 1 , M P HORTIGÓN VINAGRE M P 1 , HENAO F 1 ,
MERINO JM 1
1
UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
The tumorigenic agent 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces neurotoxic
effects that alters neurodevelopment and behavior both during development and adulthood.
There are many ongoing efforts to determine the molecular mechanisms of TCDDmediated
neurotoxicity, the signaling pathways involved and its molecular targets in neurons.
In this work, we have used SHSY5Y human neuroblastoma cells to characterize the
TCDD-induced toxicity. TCDD produces a loss of viability (EC50 = 292 ± 28 nM) linked to an
increased caspase-3 activity, PARP-1 fragmentation, DNA laddering and nuclear fragmentation,
in a similar way than staurosporine, a prototypical molecule of apoptosis induction.
In addition, TCDD produces a decrease of mitochondrial membrane potential and an increase
of intracellular calcium concentration. Finally, based on the high lipophilic properties of
the dioxin, we test the TCDD effect on the membrane integrity using sarcoplasmic reticulum
vesicles as a model. TCDD produces calcium efflux through the membrane and an anisotropy
decrease that reflects an increase in membrane fluidity. Altogether these results support
the hypothesis that TCDD toxicity in SHSY5Y neuroblastoma cells provokes the disruption
of calcium homeostasis, probably affecting membrane structural integrity, leading to an
apoptotic process.
P-04
CHILDHOOD SOLID TUMOURS SURVIVAL IN SPAIN 1980-2006:TIME
TRENDS AND VARIATIONSBY AGE AND SEX
FELIPE-GARCÍA S 1 , SÁNCHEZ DE TOLEDO-CODINA J 2 , ACHA GARCÍA T 3 , SASTRE–URGELLES A 4 ,
NAVAJAS GUTÍERREZ A 5 , PERIS-BONET R 1
1
REGISTRO NACIONAL DE TUMORES INFANTILES. UNIVERSITAT DE VALENCIA (RD06/0020/0033)
2
SERVICIO DE ONCOLOGÍA Y HEMATOLOGÍA PEDIÁTRICA. HOSPITAL UNIVERSITARIO VALL D’HEBRON,
BARCELONA (RD06/0020/1021)
3
UNIDAD DE ONCOLOGÍA PEDIÁTRICA. HOSPITAL MATERNO INFANTIL CARLOS HAYA, MÁLAGA
4
SERVICIO DE ONCOLOGÍA INFANTIL. HOSPITAL LA PAZ, MADRID
5
UNIDAD DE ONCOLOGÍA INFANTIL. HOSPITAL DE CRUCES. BARACALDO, BIZCAIA
Objectives: To document time trends and variations by age and sex of 5-year survival in
childhood solid tumours in Spain.
Material and methods: Retrospective hospital-based (paediatric oncology units) cohort
study. Subjects were 9383 children, aged 0-14 years, diagnosed in 1980-2006 with an incident
solid tumour (Groups III to XII of the International Classification of Childhood Cancer).
Periods 1980-2006 and 1990-2006 were analyzed for trends; and 1995-2004 for comparisons
by sex and age. Observed survival was estimated by Kaplan-Meier method for cohorts
defined by year of incidence. 5-year follow-up after diagnosis was active. Differences by sex
and age, and trends were tested with the log-rank and the log-rank for trend respectively.
Results: Overall survival of solid tumours increased significantly (p

P-05
SOX11 REGULATES PAX5 EXPRESSION AND BLOCKS TERMINAL B-CELL
DIFFERENTIATION IN AGGRESSIVE MANTLE CELL LYMPHOMA
VEGLIANTE MC 1 , PALOMERO J 1 , NAVARRO A 1 , CAMPO E 1 , AMADOR V 1
1
INSTITUT D’INVESTIGACIONS AUGUST PI I SUNYER – IDIBAPS (RD06/0020/0039)
Mantle cell lymphoma (MCL) is one of the most aggressive lymphoid neoplasms whose
pathogenesis is not fully understood. The neural transcription factor SOX11 is constantly
overexpressed in virtually all aggressive MCLs, and at lower levels in a subgroup of Burkitt
lymphomas and acute lymphoblastic lymphomas but not in other lymphoid neoplasms or
normal lymphoid cells. In contrast to aggressive MCL, SOX11 is totally absent in patients
with an indolent clinical outcome of the disease.
Its highly specific expression in aggressive MCL suggests that it may be an important element
in the development and progression of this tumour.
In the present study, we show that SOX11 promotes tumor growth in a MCL-xenotransplant
mouse model.
Genome-wide ChIP-chip analysis and gene expression profiling (GEP),after SOX11 silencing
in MCL cell lines, revealed target genes and transcriptional programs regulated by SOX11
including the block of mature B-cell differentiation, modulation of cell cycle, apoptosis and
stem cell development. PAX5 emerges as one of the major SOX11 direct targets. SOX11
silencing downregulates PAX5, induces BLIMP1 expression and promotes the shift from a
mature B-cell into the initial plasmacytic differentiation phenotype, in both primary tumor
cells and in an in vitro model.
Our results suggest that SOX11 contributes to tumor development and aggressive behavior
of MCL by altering the terminal B-cell differentiation program. These findings provide an
improved understanding of the molecular mechanisms contributing to the pathogenesis of
MCL and may have clinical implications in the diagnosis of patients and selection of therapeutic
strategies more adapted to the molecular diversity of this tumor.
P-06
VEGF-R2: ¿NUEVO PREDICTOR DE METÁSTASIS EN CARCINOMA DE MER-
KEL?
CARNICERO CÁCERES S 1 , GONZÁLEZ VELA MC 1 , VAQUÉ DÍEZ JP 2 , PIRIS PINILLA MA 1
1
HOSPITAL UNIVERSITARIO MARQUÉS DE VALDECILLA (RD06/0020/0107)
2
IFIMAV-FUNDACIÓN MARQUÉS DE VALDECILLA ( RD06/0020/0107)
El carcinoma de Merkel es un agresivo carcinoma neuroendocrino de la piel. Suele aparecer
en las zonas expuestas al sol y afecta a personas mayores e inmunodeprimidos. Aunque
su frecuencia es rara, su incidencia está aumentando en los últimos años. Frecuentemente
presenta metástasis a nivel ganglionar en el momento del diagnóstico y tiene un alto índice
de recurrencia local, por lo que se han propuesto varios indicadores pronósticos, si bien los
datos presentes en la literatura son conflictivos.
Material y Métodos: Se recogieron 33 casos de los archivos del Departamento de Patología
del Hospital Universitario Marqués de Valdecilla, desde el año 1992 hasta 2011, y se
analizan tanto las características clínicopatológicas (sexo, edad, localización, tamaño, estadio,
tratamiento) como histológicas (patrón, existencia o no de ulceración o necrosis, número
de mitosis, infiltrado linfocitario, invasión vascular, distancia a márgenes quirúrgicos)
e inmunohistoquímicas de los tumores (CK20, cromogranina A, sinaptofisina, TTF-1, NM23,
VEGF-R2, p53, p63 y Ki67). El estudio de IHQ se realizó en tejido parafinado, mediante el
sistema EnVision sistema (Dako, Glostrup, Dinamarca). El estudio estadístico se realizó
usando using SPSS (V15.0) soft-ware (SPSS Inc., Chicago, IL, USA).
Resultados: Se realizó seguimiento de 31 de los 33 pacientes, con una media de 29,3
meses (rango 1-144). Diecinueve casos eran mujeres (57,6%) y 14 varones (42,4%); la
edad media fue de 77,5 años (rango:42-93).
La afectación de márgenes quirúrgicos, angioinvasión e inmunoreactividad para VEGF-R2
se correlacionaron con mayor recurrencia local y / o metástasis a distancia, si bien mediante
análisis multivariante únicamente el VEGF-R2 presentó una asociación estadística significativa,
convirtiéndole en un factor predictor independiente.
Los resultados de este estudio sugieren un posible papel de la vía de señalización de VE-
GF-R2 en la progresión del MCC y el posible beneficio del uso de los tratamientos dirigidos
contra VEGF-R2.
48 49

P-07
DIOXIN RECEPTOR KNOCK-DOWN PROMOTES PRIMARY AND TGF-INDU-
CED EPITHELIAL-MESENCHYMAL TRANSITION
RICO-LEO EM 1 , ALVÁREZ-BARRIENTOS A 1 , FERNÁNDEZ-SALGUERO PM 1
1
UNIVERSIDAD DE EXTREMADURA, BADAJOZ (R006/0020/1016)
Recent studies have highlighted the role of the dioxin receptor (AhR) in maintaining cell
morphology, adhesion and migration. Overall, those AhR functions depend on the cell phenotype
and while AhR expression maintains mesenchymal fibroblasts migration it also inhibits
keratinocytes motility.
These observations prompted us to investigate whether AhR modulates the epithelial-tomesenchymal
transition (EMT) in primary AhR + / + and AhR-/- keratinocytes and in NMuMG
cells engineered to knock-down AhR (sh-AhR) or to express a constitutively active receptor
(CA-AhR). Both AhR-/- keratinocytes and sh-AhR NMuMG cells had increased migration and
reduced levels of epithelial markers E-cadherin, -catenin together with increased amounts
of mesenchymal markers Slug/Snai2, Snail, vimentin, N-cadherin and -smooth muscle actin.
Consistently, CA-AhR NMuMG cells had reduced migration and more pronounced expression
of epithelial markers. TGF exacerbated the pro-migratory mesenchymal phenotype in
both AhR-expressing and AhR-depleted cells, although the effects on the latter were more
significant.
Rescuing AhR expression in sh-AhR cells reduced migration and Slug/Snai2 and Snail expression
and restored E-cadherin levels. Human HaCaT cells, interfered for AhR (si-AhR),
further supported the AhR-deficient EMT phenotype.
Interestingly, co-immunoprecipitation and immunofluorescence assays showed that AhR
associates with E-cadherin and -catenin in common protein complexes, arguing for the
existence of non-nuclear roles of AhR in cell migration. Thus, reducing AhR expression in
epithelial cells favors EMT, a phenotypical change potentially relevant in normal development
and in such diseases as metastatic cancer.
P-08
ANÁLISIS DE LAS ALTERACIONES CITOGENÉTICAS EN 2131 PACIENTES
CON LLC Y LBM. ESTUDIO MULTICÉNTRICO DEL GCECGH Y GELLC
PUIGGROS A 1 , COLLADO R 2 , DELGADO J 3 , HERNÁNDEZ JA 4 , HERNÁNDEZ JM 5 , SOLÉ F 1 , CARBO-
NELL F 2 , ESPINET B 1
1
HOSPITAL DEL MAR, PARC DE SALUT MAR BARCELONA (RD07/0020/2004)
2
HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA, VALENCIA
3
HOSPITAL CLÍNIC, BARCELONA
4
HOSPITAL UNIVERSITARIO INFANTA LEONOR
5
HOSPITAL UNIVERSITARIO DE SALAMANCA, SALAMANCA (RD06/0020/0006)
Introducción: Las alteraciones citogenéticas tienen valor pronóstico en la leucemia linfática
crónica (LLC), siendo las más frecuentes: del(13q), +12, del(11q) y del(17p). Existen
pocas series amplias de citogenética convencional (CC) en LLC. Respecto a la linfocitosis B
monoclonal (LBM), los estudios por FISH sugieren alteraciones similares a la LLC.
Objetivos: Valorar la incidencia de alteraciones recurrentes por CC y/o FISH, e integrarla
con datos clínico-biológicos. Desarrollar estudios derivados que analicen específicamente
alteraciones concretas.
Pacientes y Métodos: En el marco del Grupo Cooperativo Español de Citogenética Hematológica
y del Grupo Español de LLC, se han recogido los datos clínico-biológicos de 2131
pacientes con LLC/LBM. 898 presentaban datos de CC, 1835 datos de FISH (13q14, 12,
11q22.3 y 17p13) y 698 información de ambas al diagnóstico.
Resultados: Se han estudiado 1738 LLC y 393 LBM. Las principales características clínicobiológicas
y de seguimiento se recogen en la Tabla. Un 81,4% de LLC se diagnosticaron
en estadío A de Binet y un 38,8% progresaron. Un 23,4% de LBM progresaron a LLC.
La frecuencia de cariotipos alterados no difería significativamente entre LLC y LBM (36%
vs 34%). Las anomalías más frecuentes detectadas en LLC por CC eran: +12, alt. 13q,
del(11q), t(18q21), t(14q32), del(6q) y +18, +19. Por FISH, ambas entidades presentaron
porcentajes similares de +12 y del(13q). La detección de del(11q) y del(17p) fue significativamente
inferior en la LBM.
Conclusiones: 1.La frecuencia y tipo de alteraciones por CC de la serie española son
similares a los descritos en otras series de LLC. 2.El porcentaje de detección de anomalías
por FISH es ligeramente inferior al descrito por Döhner y cols (2000), especialmente
de del(11q) (9% vs 18%). 3.La incidencia de alteraciones en LBM es similar a la de LLC,
aunque las alteraciones de 11q y 17p, de mal pronóstico, son menos frecuentes. 4. La ampliación
de esta serie permitirá realizar estudios, algunos de los cuales ya están en marcha,
que analicen el impacto de alteraciones citogenéticas específicas con un tamaño muestral
adecuado.
50 51

P-09
GENETIC ABERRATIONS IN PEDIATRIC FOLLICULAR LYMPHOMA
MARTÍN GUERRERO I 1,2, SALAVERRIA I 2 , BURKHARDT B 3 , SZCZEPANOWSKI M 4 , GARCÍA-ORAD A 1 ,
BAUDIS M 5 , BENS S 2 , DE LEVAL L 6 , HORN H 7 , LISFELD J 3 , PELLISSERY S 2 , KLAPPER W 4 , OSCHLIES
I 4 , SIEBERT R 2
1
DEPARTMENT OF GENETICS, PHYSICAL ANTHROPOLOGY AND ANIMAL PHYSIOLOGY, UPV-EHU
(RD06/0020/0048)
2
INSTITUTE OF HUMAN GENETICS, UNIVERSITY HOSPITAL SCHLESWIG-HOLSTEIN, KIEL, GERMANY,
3
NHL-BFM STUDY CENTER, DEPARTMENT OF PEDIATRIC HEMATOLOGY AND ONCOLOGY, JUSTUS-
LIEBIG-UNIVERSITY, GIESSEN, GERMANY
4
DEPARTMENT OF PATHOLOGY, HEMATOPATHOLOGY SECTION AND LYMPH NODE REGISTRY, CHRIS
TIAN-ALBRECHT UNIVERSITY, KIEL, GERMAN
5
INSTITUTE OF MOLECULAR LIFE SCIENCES, UNIVERSITY OF ZURICH, ZURICH, SWITZERLAND
6
INSTITUTE OF PATHOLOGY, CHUV, UNIVERSITY HOSPITAL OF LAUSANNE, SWITZERLAND
7
DEPARTMENT OF CLINICAL PATHOLOGY, ROBERT-BOSCH-HOSPITAL AND DR. MARGARETE FISCHER-
BOSCH-INSTITUTE OF CLINICAL PHARMACOLOGY STUTTGART, GERMANY
Pediatric follicular lymphoma (FL) is a rare disease that differs from its adult counterpart
both genetically and clinically. Excluding pediatric FL with IRF4-translocation, the genetic
events associated with pediatric FL have not yet been defined. The aim of this study was to
perform a complete genetic characterization of IRF4-translocation negative pediatric follicular
lymphomas to elucidate the genetic profile of these rare pediatric cases and determine
common genetic alterations that could be associated to this phenotype.
We applied array-comparative genomic hybridization and molecular inversion probe assay
adapted to formalin-fixed paraffin-embedded tissues from 18 patients aged ≤18 years diagnosed
with FL. With the exception of one case with only focal involvement by lymphoma,
the tumor cell content exceeded 50% in the evaluable samples. Eleven of 18 patients were
treated according to NHL-BFM group multicenter trials whereas the remaining according to
different protocols. All lacked t(14;18) translocation. Mutational analysis of TNFRSF14 gene
was performed in 17 cases.
Only six pediatric cases displayed chromosomal imbalances, with gain/amplification of
6pter-p24.3 (including IRF4) and deletion/copy number neutral-loss of heterozygosity in
1p36 (including TNFRSF14) being the most frequent alterations. Sequencing of the candidate
gene TNFRSF14 at 1p36.32 showed nine mutations in seven cases.
Combination of molecular and genetic features differentiated a recurrent pattern of genomic
imbalances as well as of TNFRSF14 mutations in pediatric FL which together with other
genetic alterations distinguishes two subsets of pediatric follicular lymphomas. The first
group shows genomic aberrations and is associated with more aggressive histopathologic
and clinical features. The second group lacks genetic alterations detectable with the present
approaches and is associated with a more limited disease. Despite the absence of genomic
aberrations, these cases resembled FL by their histopathological features.
Molecular beacons in situ techniques will be used to address possible co-localization between
these proteins and transcripts derived from B1X35S and piRNAs.
Agradecimientos a otros autores: David Ivars, Ana Rodriguez-Vicente, José Ángel Hernandez, Ana
Ferrer, Eva Gimeno, Maite Ardanaz, Elisa Luño, Javier Grau, Isabel Marugán, Mar Osma, Teresa González,
Mª José Marco, Mª José Calasanz, Alberto Valiente, Eva Arranz, Ana Batlle, Ana Carla Oliveira,
Ismael Buño, José Cervera, Mª Teresa Vargas, Mª Angeles Piñán, Mª Teresa Giménez, María Talavera,
Marcos González, Anna Aventín, Eugènia Abella, Carmen Sanzo, Jordi Juncà, Mª José Jiménez, Miguel
Sagüés, Isana Benet, Mª José Terol, Francisco Ortuño, Eugenia Fernández, Intza Aoiz, Carolina Muñoz,
Javier Loscertales, Carolina Martínez-Laperche, Alicia Rodríguez, en representación del Grupo Coope-
52 rativo Español de Citogenética Hematológica (GCECGH) y el Grupo Español de Leucemia Linfática
53
Crónica (GELLC).

P-10
MOLECULAR PATHWAYS REGULATED BY ETV5 TRANSCRIPTION FACTOR
IN THE INVASION OF ENDOMETRIAL CARCINOMA
PEDROLA N 1 , COLAS C 1 , CASTELLVÍ J 2 , GIL-MORENO A 3 , XERCAVINS J 3 , REVENTÓS J 1 , RUIZ A 1
1
INSTITUT RECERCA VALL HEBRÓN, BARCELONA (RD06/0020/0058)
2
PATOLOGÍA HOSPITAL VALL HEBRÓN, BARCELONA (RD06/0020/0058)
3
GINECOLOGÍA HOSPITAL VALL HEBRÓN BARCELONA (RD06/0020/0058)
Our group has described the ETV5 transcription factor associated with the early steps of
endometrial cancer invasion. Here, we aim to identify ETV5 downstream target genes involved
in myometrial infiltration.
Material and Methods: We have performed a gene expression analysis to compare Hec1a
endometrial cancer cells against its stable population overexpressing ETV5. Statistical and
literature mining were performed to select ETV5 candidate target genes. Selected genes
were analysed by chromatin immunoprecipitation and promoter-regulation was confirmed
by luciferase reporter assays. Cell migration and invasion assays were performed to examine
the role of NID1 and NUPR1genes in Hec1A ETV5 overexpressing cells. Tumor invasion
was also analysed in an orthotopic mouse model. Finally, human endometrial tumor samples
were analysed by RTqPCR and IHC to determine levels of gene and protein expression.
Results: ChIP analysis and luciferase reporter assays confirmed NID1 and NUPR1 as ETV5
transcriptional targets. Inhibition of NID1 and NUPR1 in Hec1A cells overexpressing ETV5
reduces cell migration and invasion both in vitro and in vivo. Expression of NID1 and NUPR1
in human endometrial tumor samples shows an increase of expression in the endometrial
invasion front.
Conclusions: We have identified Nidogen1 (NID1) and NUPR1 as direct transcriptional targets
of ETV5. Both genes mediate some of the migratory and invasive capabilities induced
by ETV5 overexpression in endometrial cancer cells both in vitro and in vivo. The identification
of new players in the myometrial infiltration step represents a valuable tool for the
molecular classification of patients as well as for the design of rational target
P-11
ANÁLISIS DE LA EXPRESIÓN DE MKP1 Y MKP3 EN MUESTRAS DE
PACIENTES DE CÁNCER DE MAMA
TORMO E 1 , SÁNCHEZ L 1 , FURRIOL J 1 , FERRER J 1 , BURGUÉS O 2 , ALONSO E 1 , NAVARRO L 2 , BRAGA-
DO R 3 , ROJO F 3 , ROVIRA A 4 , ALBANELL J 4 , EROLES P 1 , LLUCH A 5
1
FUNDACIÓN INVESTIGACIÓN CLÍNICO VALENCIA / INCLIVA (RD06/0020/0080)
2
SERVICIO DE PATOLOGÍA, HOSPITAL CLÍNICO UNIVERSITARIO DE VALENCIA
3
FUNDACIÓN JIMÉNEZ DÍAZ
4
CANCER RESEARCH PROGRAM, IMIM-HOSPITAL DEL MAR, BARCELONA (RD06/0020/0109)
5
SERVICIO DE HEMATOLOGÍA Y ONCOLOGÍA, HOSPITAL CLÍNICO UNIVERSITARIO DE VALENCIA
(RD06/0020/0080)
El cáncer de mama es el tumor maligno más frecuente entre las mujeres de todo el mundo.
Entre las nuevas dianas terapéuticas recientemente propuestas se encuentra la familia de
las MKPs (mitogen-activated protein kinase phospaphatases) conocidas también como fosfatasas
de especificidad dual. El miembro prototipo de esta familia, MKP-1, es una fosfatasa
nuclear inducible capaz de desfosforilar MAPKs (ERK, JNK, y p-38). Las MAPKs (mitogenactivated
protein kinase), los sustratos de MKPs, juegan un papel importante en proliferación,
respuestas a estrés, apoptosis, y respuesta inmune, y se ha visto que MKP-1 y MKP-3
pueden desempeñar un papel importante en tumorigénesis y contrarrestar la citotoxicidad
de varios agentes anticancerígenos.
En este trabajo se estudió la expresión de MKP-1 y MKP-3 en muestras parafinadas de pacientes
en terapia adyuvante y neoadyuvante, en tumores primarios y sus recaídas metastásicas,
así como la expresión en muestras de tejido sano. Se obtuvo el cDNA y se analizó
mediante PCR real-time por el método ΔCt. Los resultados se analizaron estadísticamente
mediante el test de kruskal –Wallis.
Se observó un descenso generalizado de la expresión de MKP-1 y MKP-3 en las muestras
de tejido tumoral respecto a las muestras de tejido sano. La expresión de MKP-1 y MKP-3
aumentó en las recaídas metastásicas respecto a sus parejas primarias. En las muestras de
terapia neoadyuvante, MKP-1 aumentó significativamente (p=0,009) en las muestras procedentes
de cirugías respecto a sus parejas de biopsias, mientras que MKP-3 no presentó
cambios significativos.
Conclusiones: MKP-1 y MKP-3 se encuentran infraexpresadas en muestras tumorales.
Las muestras procedentes de pacientes tratadas, bien sean metástasis o cirugía en el caso
de tratamiento neoadyuvante, presentan aumento de los niveles de expresión de MKP-1
respecto a sus parejas previo tratamiento. MKP-3 incrementa su expresión en las muestras
metastásicas respecto al tumor primario.
54 55

P-12
HETEROGENEITY OF CANCER-ASSOCIATED FIBROBLASTS FROM HUMAN
PRIMARY COLON TUMORS IN THEIR PRO-TUMOROGENIC ABILITIES ON
CANCER CELLS
HERRERA M 1 , HERRERA A 1 , B.M.M.K. ISLAM A 2 , BONILLA F 1 , PEÑA C 1
1
HOSPITAL U. PUERTA DE HIERRO-MAJADAHONDA (RD06/0020/0020)
2
UNIVERSIDAD DE DHAKA, DHAKA 1000, BANGLADESH
Cancer associated-fibroblasts (CAFs) constitute the major component of the tumor stroma.
CAFs actively participate in reciprocal communication with the tumor cells and with other
cell types of the microenvironment, contributing to a tumor-permissive neighborhood and
promoting tumor progression. The aim of this study is the characterization of CAFs from
primary human colon tumors regarding their ability to promote tumorogenesis.
Primary CAFs cultures were established from 15 primary human colon tumors. Purity of
primary fibroblast was evaluated by the expression of different epithelial and myofibroblasts
specific markers by RT-PCR and inmunofluorescence. CAFs were co-cultured with LIM1215
and SW480-ADH tumor colon cells to evaluate their abilities to induce migration. Also,
collagen gel contraction capacity and the expression of putative stem cell markers were
examined in different fibroblast cultures. For further classification, gene expression profile
was analyzed by microarray analysis.
Heterogeneity of α-sma expression was observed in established primary colon CAFs among
different individuals. Co-culture assays of primary CAFs with tumor colon cells showed
significant differences of fibroblasts-derive paracrine pro-migratory effects on cancer cells.
Thus, primary CAFs were grouped regarding their ability to promote tumor migration. Also,
an association between collagen gel contraction and pro-migratory effects of primary CAFs
was observed. Preliminary results from microarray data, α-sma expression and stem cells
markers analyzed indicated association between the groups based on the information of
gene expression and the different promoting migration groups.
The CAFs population from the colon tumor microenvironment is heterogeneous regarding
different patients presenting different pro-tumorogenic abilities, providing us the chance to
search for new cross-talk mediators between fibroblasts and tumor cells that finally could
be blocked to inhibit tumor progression.
P-13
ACADESINE EXERTS ANTITUMORAL ACTIVITY AND COOPERATES WITH
RITUXIMAB IN IN VITRO AND IN VIVO MODELS OF MANTLE CELL
LYMPHOMA
MONTRAVETA A 1 , CAMPO E 2 , ROUÉ G 1 , COLOMER D 1
1
HOSPITAL CLÍNIC-IDIBAPS, BARCELONA (RD06/0020/0014)
2
HOSPITAL CLÍNIC-IDIBAPS, BARCELONA (RD06/0020/0039)
Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm characterized by the t(11;14)
(q13:q32) that involves cyclin D1 overexpression. Tipically, MCL is characterized by relative
short survival, and poor outcome. Despite this, some cases displays non-nodal leukemic
disease with predominantly hypermutated IgVH, non-complex karyotypes and low or no
expression of SOX11. This indolent variant (iMCL) shows a less aggressive clinical course
that might be managed more conservatively than the conventional subtype (cMCL), which
treatment remains a challenge. Acadesine is a nucleoside analogue initially developed as a
cardioprotective agent, and which has shown a wide range of metabolic effects, including
the activation of AMP-activated protein kinase (AMPK). Acadesine was reported to induce
apoptosis in primary cells from several B lymphoid neoplasms and has been finished powerfully
a phase I/II clinical trial with relapsed/refractory chronic lymphocytic leukemia (CLL)
patients.
To evaluate the antitumoral properties of acadesine in MCL, we exposed a set of 15 MCL
primary cultures and 9 MCL cell lines for up to 48h with increasing doses of the drug. In
both MCL cell lines and MCL primary cultures, we observed a heterogeneous response,
with no correlation to common genetic alterations. Among MCL primary cultures, Acadesine
showed selective cytotoxic activity against malignant B cells while sparing accompanying T
cells. Of note, those cases corresponding to iMCL group showed increased sensitivity to the
drug, when compared to conventional MCL cases (p=0.014).
In drug combination assays, Acadesine showed a synergistic effect when combined with
the anti-CD20 monoclonal antibody Rituximab. The Acadesine-Rituximab combination also
blocked tumor growth in a cell line derived xenograft mouse model. By performing gene
profile analysis of these tumors, we found that the combination down-regulates signatures
related with cell cycle, inflammatory response and cell proliferation, suggesting that
Acadesine-Rituximab combination may represent a new approach for this entity.
Observaciones: This work was supported by grants from Ministerio de Ciencia y Innovación
(SAF 09/9503) (to DC), Redes Temáticas de Investigacion Cooperativa de Cáncer from
the Instituto de Salud Carlos III (RED 2006-20-014 and 079) (to DC and EC), and Fondo de
Investigación Sanitaria (CP07/00072 and PI09/00060) (to GR). AM is the recipient of a FPI
pre-doctoral fellowship from Ministerio de Ciencia e Innovación.
The laboratory expenses of this study were covered in part by a research contract from
Advancell Therapeutics, Advancell-Advanced In Vitro Cell Technologies S.A.
56 57

P-14
AICAR INDUCES BAK/BAK-DEPENDENT APOPTOSIS THROUGH UP-REGU-
LATION OF THE BH3-ONLY PROTEINS BIM AND NOXA IN MOUSE EMBRYO
FIBROBLASTS
MONCUNILL-MASSAGUER C 1 , GONZÁLEZ-GIRONÈS D 1 ,IGLESIAS-SERRET D 1 , COSIALLS AM 1
PÉREZ-PERARNAU A 1 , MARIELA-PALMERI C 1 , RUBIO-PATIÑO C 1 , VIOLLET B 2 , PONS G 1 , VILLUNGER
A 3 , GIL J 1
1
DEPARTAMENT DE CIÈNCIES FISIOLÒGIQUES II, INSTITUT D’INVESTIGACIÓ BIOMÈDICA DE
BELLVITGE (IDIBELL)–UNIVERSITAT DE BARCELONA, L’HOSPITALET DE LLOBREGAT, CATALUNYA,
(RD06/0020/0097)
2
INSTITUT COCHIN, UNIVERSITÉ PARIS DESCARTES, CENTRE NATIONAL DE LA RECHERCHE SCIENTI-
FIQUE (CNRS), PARIS, FRANCE
3
DIVISION OF DEVELOPMENTAL IMMUNOLOGY, BIOCENTER, INNSBRUCK MEDICAL UNIVERSITY,
INNBRUCK, AUSTRIA
AICAR triggers apoptosis independently of AMPK and p53 through the upregulation of the
BH3-only proteins BIM and NOXA in chronic lymphocytic leukemia (CLL) cells. However,
it remains unknown how AICAR treatment modulates the expression of these BH3-only
proteins.
Here we propose mouse embryonic fibroblasts (MEFs) as a useful model to analyze the
mechanism of AICAR-induced apoptosis. ZMP formation is required for AICAR-induced
apoptosis and it activates its main target Ampk. Nevertheless, direct Ampk activation with
A-769662 failed to induce apoptosis in MEFs, and AICAR also potently induced apoptosis
in Ampkα1-/-/α2-/- MEFs, demonstrating an Ampk-independent mechanism of cell death.
Notably, MEFs double knockouot for Bax and Bak were completely resistant to the apoptosis
triggered by AICAR, confirming the involvement of the mitochondrial pathway in its mechanism
of action. Apoptosis was preceeded by ZMP-dependent but Ampk-independent modulation
of mRNA levels of different Bcl-2 family members, including Noxa, Bim and Bcl-2.
Bim protein levels are accumulated by AICAR treatment of MEF cells, suggesting its role in
the apoptotic process. Strikingly, MEFs lacking both Bim and Noxa display high resistance to
AICAR, in concordance with their requirement for AICAR-induced cell death B lymphocytes.
Overall, we demonstrate that AICAR mechanism of apoptosis is highly similar in MEFs,
mouse B lymphocytes and CLL cells and thus MEFs will be used for the complete elucidation
of AICAR-induced apoptosis mechanism.
P-15
DETERMINATION OF SNAIL1 PARACRINE FUNCTIONS: IMPLICATION
IN PRO-TUMOROGENIC ABILITIES ON COLORECTAL EPITHELIAL CELLS
LINES
HERRERA-TEJERO A 1 , HERRERA-TORRES M 1 ,GARCÍA DE HERREROS A 1 , BONILLA-VELASCO
F 1 , PEÑA-MAROTO 1
1
HOSPITAL UNIV. PUERTA HIERRO-MAJADAHONDA (RD06/0020/0020)
Experimental data support the idea that the active recruitment of stromal cells by tumor
cells is essential for the generation of a microenvironment that actively fosters tumor
growth. Snail1 is a transcriptional factor that plays an important role in epithelial-mesenchymal
transition (EMT)-mediated metastasis through the regulation of E-Cadherin expression.
E-Cadherin is downregulated in human colon epithelial cells when co-cultured with Snail1
expressing cells. Moreover, expression of Snail1 in the tumor stroma correlates with lower
specific survival of cancer patients. The aim of this study was to determine the possible
pro-tumorogenic paracrine functions of Snail1 expressing cells.
Cancer-Associated Fibroblasts (CAFs) and Normal Fibroblasts (NFs) were isolated from 15
primary human colon tumors and 5 normal mucosa respectively. Colon cancer cell lines
SW480-ADH or LIM1215 were co-cultured with a panel of Snail1 expressing colon and
fibroblasts cell lines, or primary CAFs, to study migration and proliferation changes. Coculture
analyses were developed using trans-well culture system. Proliferation assays were
also analyzed with conditioned medium from fibroblasts and CAFs. The Snail1 expressing
cell lines induced higher cell migration of SW480-ADH or LIM1215 compared with Mock
cells. Moreover, increase of proliferation index in SW480-ADH cells were observed when
co-cultured with Snail1 expressing cells. In both migration and proliferation, the effect was
higher when Snail1 was expressed by fibroblasts, regarding tumor colon cells. Analysis of
primary CAFs showed higher Snail expression levels in CAFs compared with NFs. Interestingly,
co-culture of CAFs with LIM1215 or SW480-ADH cells induced a significant increase in
epithelial cell migration, as well as in proliferation, associated with Snail expression.
Together, these experiments demonstrate the Snail1-dependent paracrine pro-tumorogenic
effects of fibroblasts on colon cancer cells. Future analysis will include cytokine profile study
of Snail1 expressing cells, as well as primary CAFs and NFs, to characterize the cross-talk
between colorectal cancer cells and fibroblasts.
58 59

P-16
MEAT CONSUMPTION AND OESOPHAGEAL ADENOCARCINOMA RISK IN
THE EPIC COHORT
LUJAN-BARROSO L 1 , JAKSZYN P 1 , AGUDO A 1 , GONZÁLEZ SVATETZ CA 1
1
ICO/IDIBELL, BARCELONA (RD06/0020/0091)
Background: Previous analysis from our group based on only 65 oesophageal adenocarcinomas
cancer (OAC) cases suggest a positive association with processed meat and an
unexpected positive association with poultry. Very little information is available regarding
different types of meat intake and OAC in prospective studies.
Objetive: To assess the association between meat intake (red, white and processed
meat) and OAC. Estimate the substitution effect of different types of meat.
Methods: The EPIC study is a study designed to investigate the relationships between diet,
lifestyle, and environmental factors and the incidence of cancer carried-out in 23 centres
from 10 European countries. Meat intake was estimated based on country-specific food
questionnaires. The hazard ratios (HRs) and their corresponding 95% confidence intervals
(CIs) for the development of OAC cancer were estimated using the Cox proportional
hazards model. Meat intake is presented as 25g/2000kcal. All models were adjusted for
BMI, sex, smoking status, educational level, total fruits and vegetables, alcohol and energy
intake. Additive model was constructed to evaluate: 1. additive effect (the risk associated
with to adding the amount of red meat while white meat remains constant). 2. Substitution
effect (the effect of substitution red meat for white meat while keeping total meat
intake constant).
Results: The association between total meat intake and OAC was statically significant
(HR: 1.16, 95%CI=1.07-1.27). Additive models shows a positive significant effect of white
meat (HR: 1.22, 95%CI=1.03- 1.45) and processed meat (HR: 1.18, 95%CI= 1.02-1.37).
None substitution effect were found for any meat-type.
Conclusion: We have found a positive significant association between processed meat
intake and OAC and a non significant association with red meat intake. An unexpected statically
significant increase of the risk due to white meat intake was observed. Further studies
with large sample size are needed in order to clarify these findings
P-17
ΔNP73 UPREGULATION CORRELATES WITH POOR PROGNOSIS OF COLON
CANCER PATIENTS
SAN MILLÁN BLANCO C 1 , SOLDEVILLA NAVARRO B 1 , GIL CALDERÓN B 1 , BONILLA VELASCO F 1 ,
DOMÍNGUEZ MUÑOZ G 1
1
HOSPITAL UNIV. PUERTA DE HIERRO-UAM, MADRID (RD06/0020/0020)
Cumulative data support the role of ∆TAp73 variants in tumorigenic processes such as drug resistance.
We evaluate the impact of TP73 isoforms and their putative target genes ABCB1, HMGB1
and CASP1 on the survival of colon cancer patients and the correlation between their expressions.
We determined in 77 colon cancer patients the expression of Ex2p73, Ex2/3p73, ΔNp73, TAp73,
ABCB1, HMGB1 and CASP1 by RT-PCR. Tumor characteristics, disease-free survival (DFS) and
overall survival (OS) were examined in each patient. Additionally, functional experiments were
performed to check whether ectopic expression of ∆Np73 modifies the proliferation, drug resistance,
migration and invasion properties of colon tumor cells and the expression of ABCB1,
HMGB1 and CASP1.
Positive correlations were observed between the expression levels of ∆TAp73 variants and HMGB1.
A trend was also observed for ABCB1. Over-expression of ΔEx2/3p73 and ΔNp73 isoforms significantly
associated with advanced stages (p = 0.04 and p = 0.03, respectively) and predicted
shortened OS (p = 0.04 and p = 0.05, respectively). Similarly, high levels of ABCB1 and HMGB1
associated with shorter OS (p = 0.04 and p = 0.05, respectively). Multivariate analysis showed
that, in addition to the tumor stage, ABCB1 and HMGB1 had independent relationships with OS
(p = 0.008). Ectopic expression of ∆Np73 associated with an increase in proliferation and drug
resistance. The positive correlation between ∆TAp73 variants and HMGB1 and ABCB1 expression
supports them as TP73 targets. The fact that upregulation of ∆TAp73 isoforms associated with
shortened OS, increase in proliferation and drug resistance confirms their oncogenic role and
plausible value as prognostic markers.
ABCB1 and HMGB1, putative ∆TAp73 target genes, strongly predict OS in an independent manner,
making clear the importance of studying downstream TP73 targets that could predict the outcome
of colon cancer patients better than ∆TAp73 themselves do.
60 61

P-18
DIFFERENT EXOSOME CARGO FROM PLASMA/BRONCHOALVEOLAR LAVAGE IN
NON-SMALL-CELL LUNG CANCER
RODRÍGUEZ MORENO M 1 , SILVA LEAL FJ 1 , SOLDEVILLA NAVARRO B 1 , HERRERA TORRES M 1 ,
GARCÍA BARBERÁN V 1
1
FUNDACIÓN PARA LA INVESTIGACIÓN BIOMÉDICA DEL HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-
MAJADAHONDA MADRID (RD06/0020/0020)
Exosomes were isolated and characterized in plasma and bronchoalveolar lavage from patients
with non-small-cell lung cancer and from patients with several pulmonary diseases.
Exosomes from 30 and 75 patients with tumour and non-tumour pathology were quantified
by acetylcholinesterase activity and characterized by Western Blot and Confocal Microscopy.
Differences in exosome cargo were analyzed by miRNA PCR and human protein cytokine
arrays.
Exosomes were detected in greater amounts in plasma than in BAL in both pathologies
(p

P-20
THE POLARITY GENE PARD3 IS INACTIVATED IN SQUAMOUS CELL
CARCINOMAS OF THE LUNG
BONASTRE E 1 , ZONDERVAN I 2 , FACCHINETTI F 3 , CONDOM E 4 , SIDRANSKY D 5 , ROZ L 3 , SAVOLA
S 2 , SÁNCHEZ-CÉSPEDES M 1
1
IDIBELL, BARCELONA (RD06/0020/0062)
2
MRC-HOLLAND, NETHERLANDS
3
GINECOLOGÍA HOSPITAL VALL HEBRÓN BARCELONA (RD06/0020/0058)
4
HOSPITAL DE BELLVITGE, BARCELONA
5
JOHNS HOPKINS UNIVERSITY SCHOOL
In spite of the recent advances in cancer genomics, the genetics underlying the development
of lung squamous cell carcinomas (SCC) is still poorly understood. To get insights
into the genes that contribute to lung SCCs we tested for alterations at the cell polarity
related gene, PARD3, in a panel of 58 lung cancer cell lines from various histopathologocial
subtypes. The analysis confirmed an intragenic deletion in a SCC cell line, this and other
informations circumscribed PARD3 alterations to this lung cancer type. Next, we extended
the genetic screening, which also included the determination of intragenic deletions by
multiplex ligation-dependent probe amplification assay, to 107 primary lung SCCs. Six per
cent of the tumors endured biallelic and tumor-specific alterations at PARD3. The absence
of PAR3 protein was evident in those tumor carrying frameshift mutations or intragenic
deletions, while high levels and abnormal immunostaining of PAR3 were observed in some
PARD3 wild type tumors. Since some PARD3 alterations lead to aminoacid changes or predicted
for shorter proteins, we decided to evaluate how these affect the normal function
of the PAR3 protein. Our results clearly evidenced that, in contrast to mutants, only the
wild type PAR3 proteins restituted the formation of tight junctions, clearly evidencing that
these mutations affect the correct function of the protein. In conclusion, the presence of
deleterious mutations at PARD3 attest to its relevance in the development of lung SSCs.
P-21
FUNCTIONAL ANALYSIS OF THE GATA2 PROMOTER SHOWS THAT MUTA-
TIONS OF GATA2 IMPAIR ITS OWN TRANSCRIPTIONAL REGULATION
CORTÉS LAVAUD X 1 , MAICAS M 1 , VÁZQUEZ I 1 , VICENTE C 1 , URQUIZA L 1 , GARCÍA SÁNCHEZ
MA 1 , ODERO MD 1
1
CENTRO DE INVESTIGACIÓN MÉDICA APLICADA (CIMA), PAMPLONA (RD06/0020/0078)
GATA2 encodes a transcription factor with essential functions in hematopoiesis. Recent
studies report mutations in GATA2 in familial syndromes characterized by predisposition to
myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
It has been showed in murine models that GATA2 activates its own transcription by binding
to regions located at -2.8 and -1.8 kb from the transcription start site (TSS). Thus, we hypothesized
that these GATA2 mutations could alter the GATA2 autoregulatory loop, affecting
the transcription of GATA2. Bioinformatic analysis showed two regions in the human GATA2
promoter, with two putative GATA2 binding sites. ChIP-qPCR assays showed that GATA2
binds to these sites.
To assess the ability of both wild-type and GATA2 mutations to regulate its own transcription,
we transfected these GATA2 gene variants along with different GATA2 promoter
constructs into HEK293T cells, and performed luciferase reporter assays. Wild-type GATA2
activated its transcription through the -2.4 kb site; however, it was not able to activate the
full length promoter construct containing both the -3.4 and -2.4 sites. CEBPA binding sites
near the -3.4 site could explain these results.
The T354M mutant activated GATA2 transcription in a similar manner than the GATA2 wildtype,
raising the question about the complex function of T354M. On the contrary, del355T
was unable of sustain any activation of GATA2.
Finally, the L359V mutation, present in 10% of CML cases with blast crisis, was able to activate
the GATA2 promoter, even the full length promoter construct that contains both -3.4
and -2.4 sites, supporting that L359V is a gain-of-function mutation.
In summary, GATA2 mutations had different effects on the GATA2 promoter that could
affect the dose of GATA2 and therefore, of other GATA2 targets. Studies to further clarify
these questions are in progress.
64 65

P-22
ÍNDICE DE RIESGO BASADO EN GENES ANGIOGÉNICOS. VALOR PRONÓS-
TICO EN PACIENTES CON CÁNCER DE PULMÓN NO MICROCÍTICO (CPNM)
RESECABLE
SANMARTÍN E* 1 , USÓ M* 1 , MARTÍNEZ A 1 , SIRERA R 1 , MARTORELL M 1 , GUIJARRO R 1 , BLASCO A 1 ,
JANTUS-LEWINTRE E 1 , CAMPS C 1
1
HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA, VALENCIA (RD06/0020/1024)
*AMBAS DEBEN CONSIDERARSE CO-AUTORAS
La angiogénesis es un mecanismo clave en el crecimiento y progresión tumoral regulada
principalmente por los miembros de la familia VEGF. En este trabajo se analizó la expresión
de 11 genes angiogénicos en una cohorte de pacientes con CPNM y se correlacionaron los
niveles de expresión con las variables clinicopatológicas y pronósticas.
Material y métodos:
Se analizaron 175 muestras de tumor y tejido normal adyacente de pacientes con CPNM, a
partir de las cuales se extrajo el ARN. La cuantificación génica se realizó mediante RT-qPCR
para los siguientes genes: HIF1-A, PIGF, VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGFR-1, VE-
GFR-2, VEGFR-3, NRP1 y NRP2. La expresión génica relativa se calculó mediante la fórmula
de Pfaffl.
Resultados:
Las muestras tumorales presentaron sobreexpresión de PlGF e infraexpressión de VEGF-D,
VEGFR2 y VEGR3 en comparación con el tejido normal (2.76x, 0.035x, 0.417x y 0.426x,
respectivamente). Los análisis de supervivencia revelaron que los pacientes con niveles
de expresión de VEGF-A o PlGF elevados, así como aquellos con valores de expresión de
VEGF-B o VEGF-D bajos presentan un peor pronóstico tanto en tiempo a la progresión
(TLP) (p=0.024, p=0.027, p=0.020 y p=0.135 respectivamente) como en supervivencia
global (SG) (p=0.055, p=0.048, p=0.020 y p=0.135, respectivamente). En base a estos
resultados se propone un modelo de Índice de Riesgo Angiogénico. Tanto el TLP como la
SG son significativamente diferentes entre los pacientes con valores bajos, medios o altos
de este índice (ver Tabla 1).
Conclusiones:
La expresión de los miembros de la familia de VEGF modula los procesos de angio y linfangiogénesis
en CPNM. Se han encontrado diferencias en la expresión de 4 genes en tumor
con respecto a estroma. Además se ha establecido un índice de riesgo angiogénico que
clasifica a los pacientes según su pronóstico. (Financiado en parte por ISCIII: PS09-01149
y RD06/0020/1024.)
Tabla 1: TLP y SG según los grupos de riesgo.
P-23
ETV5 REGULATES IGCAMS SUPERFAMILY DURING MYOMETRIAL INVA-
SION
DEVIS JAUREGUI L 1 , CAMPOY I 1 , PEDROLA N 1 , ALONSO-ALCONADA L, CASTELLVÍ J 1 , ABAL M 2
REVENTÒS J 1 , COLÁS E 1
1
INSTITUT RECERCA VALL HEBRÓN, BARCELONA (RD06/0020/0058)
2
CHUS, SANTIAGO DE COMPOSTELA
Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female
genital tract, with myometrial invasion representing an increase in the rate of recurrences
and a decrease in survival for the most common subtype, the endometrioid EC. We have
previously identified an ETS transcription factor, ETV5, associated with myometrial infiltration
in human ECs through the promotion of EMT, regulation of metalloproteinases and
protection against the oxidative stress.
A cDNA microarray study, comparing Hec1a cells and its stable population overexpressing
ETV5, analyzed gene expression patterns on a whole-genome scale. Bioinformatics analysis
evidenced that ETV5 promotes EMT and pointed to cell adhesion, cell-cell contact and
cellular junctions, and actin cytoskeleton reorganization. One of the main families of this
molecular cells adhesions altered was the Immunoglobulin superfamily (IgCAMs). IgCAMs
have been described as key mediators of cell-cell and cell-matrix adhesion. The differential
expression of selected genes was validated by qRT-PCR, immunobloting and immunofluorescence
when comparing Hec1a against its stable population overexpressing ETV5.
We identified that ETV5 regulates the expression of the selected genes through ChIP and
luciferase-reporter assays. We performed qRT-PCR and immunohistochemistry on tissues of
eleven independent non invasive and invasive ECs to characterize Ig-CAMs expression and
validate ETV5 regulation through Chip-on-Chip assay. We concluded that ETV5 overexpression
modulates the IgCAMs profile at transcriptional and protein levels binding to ICAM2,
NrCAM, and ALCAM promoters both in EC cells and tissues..
66 67

P-24
NOX4 PLAYS A TUMOR SUPRESSOR ROLE IN HEPATOCELLULAR
CARCINOMA CELLS
Crosas-Molist E 1 , Bertran E 1 , Fernando J 1 , Fabregat I 1, 2
1
IDIBELL, BARCELONA (RD06/0020/0097)
2
UNIVERSIDAD DE BARCELONA, BARCELONA
Introduction and AIMS: NOX4 has been implicated in a variety of physiological processes,
including cellular senescence, apoptosis, survival, migration, endoplasmic reticulum
stress, and differentiation (Brown and Griendling, Free Radic Biol Med. 2009). In liver cells,
NOX4 upregulation is necessary for TGF-beta-induced suppressor effects, in particular, for
cell death (Carmona-Cuenca et al., J Hepatol. 2008; Caja et al., Cancer Res. 2009). In order
to analyze whether NOX4 may play a general tumor suppressor role in liver tumorigenesis,
we have analyzed the effect of NOX4 knock-down in human HCC (hepatocellular carcinoma)
cell lines.
Results: Stable silencing of NOX4 conferred an increased proliferative capacity to HCC
cell lines, as proved through a DNA synthesis assay and by impedance measurement of
attached cells through time (Roche xCELLigence System). Caspase-3 activity assay was performed
in order to analyze basal cell death, showing decreased apoptosis in silenced cells
when compared to control cells. Interestingly,NOX4 silencing increased migration capacity.
This finding was in accordance to a diminished cell-ECM (Extracellular Matrix) adhesion
capacity, important for individual migration. Cell-to-matrix adhesion was analyzed by impedance
measurement in different substrates such as an inert matrix, collagen I, collagen
IV and fibronectin. Results showed a decreased adhesion capacity of the silenced cells in
all the substrates studied. Moreover, Vinculin and p-FAK immunofluorescence showed a
different pattern in NOX4 knock-down cells in comparison to control cells. Finally, stable
silencing of NOX4 increased the tumorigenic capacity of HCC cells after subcutaneous injection
of them into Balb c/Nude mice.
Conclusion: Stable silencing of NOX4 in HCC cells confer them a more malignant phenotype,
since they show increased cell proliferation and decreased basal apoptosis. Simultaneously,
a more invasive phenotype is observed, with decreased cell-to-cell contact and
cell-to-matrix attachment, and increased migration. In summary, NOX4 may play a relevant
tumor suppressor role in liver tumorigenesis.
P-25
AhR BINDING TO Alu ELEMENTS X14S, X36S AND X45S MODULATES THE
EXPRESSION OF STEMNESS-RELEVANT GENES Oct4, Nanog, Shh AND Sox2
GONZÁLEZ RICO FJ 1 , ÁNGEL CARLOS ROMÁN 2 , PEDRO M. FERNÁNDEZ SALGUERO 1
1
UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
2
INSTITUTO CAJAL, CSIC
Eukaryotic genomes are organized into expression domains whose activity depends on
local chromatin structure. To accomplish that, functional gene clusters are defined by the
binding of transcription factors to conserved regulatory sequences. Transposable elements
are no longer considered parasite mobile sequences; instead they seem to regulate gene
expression by modulating genome organization and stability. Such transposon functions are
likely associated to their ability to bind specific transcription factors.
We have previously reported that a genome-wide SINE-B1 retrotransposon (B1-X35S) has
a potent insulation activity by binding of the transcription factors dioxin receptor (AhR) and
Slug (Snai2) to their consensus elements present in the transposon sequence. In the human
genome, three Alu elements have been identified that are heterologous to the B1-X35S
mouse transposon and that contains a conserved AhR binding site. Interestingly, these Alus
(hereafter X14S, X36S and X45S) are present in most stemness-relevant genes including
Oct4, Nanog, Shh, Sox2 and Notch1.
In the undifferentiated embryonic carcinoma Ntera-2 cell line, treatment with retinoic acid
(RA) induces differentiation by decreasing Oct4, Nanog and Shh expression levels. Remarkably,
RA-induced differentiation promotes a parallel increase in AhR protein. Silencing
of AhR by RNA interference (siRNA of shRNA) blocks the decrease in Oct4, Nanog and Shh
induced by RA thus maintaining an undifferentiated state. Chromatin inmunoprecipitation
(ChIP) experiments were performed to confirm AhR binding to the X14S, X36S and X45S
Alu elements present in the promoter of such target genes. In addition, enhancer blocking
assays (EBAs) will be used to address the insulator activity of X14S, X36S and X45S Alu
elements. Their insulator activity will be confirmed in vivo in zebrafish.
We suggest that X14S, X36S and X45S Alu elements can represent evolutionary conserved
genome-wide insulators activated by the transcription factor AhR to control developmental,
oncogenic or toxicological-dependent processes.
This work was supported by grants from Ministerio de Economía y Competitividad
(BFU2009-07219 and ISCIII-RTICC: RD06/0020/0097) and Generalitat de Catalunya
(2009SGR312). EC is recipient of a FPU fellowship from Ministerio de Educación, Cultura
y Deporte
68 69

P-26
SECUENCIACIÓN DE ALTO RENDIMIENTO PARA LA CARACTERIZACIÓN
DEL MIRNAOMA EN CPNM EN ESTADIOS INICIALES. ANÁLISIS DE EXPRE-
SIÓN DIFERENCIAL
GALLACH S 1 , JANTUS-LEWINTRE E 1 , USÓ M 1 , FIGUEROA S 1 , MONTANER D 2 , MARTINEZ CHAN N 1 ,
HERNANDO C 1 , CAMPS C 1
1
HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA, VALENCIA (RD06/0020/1024)
2
CENTRO INVESTIGACIÓN PRÍNCIPE FELIPE, VALENCIA
Introducción: Los miRNAs están siendo estudiados como posibles biomarcadores en cáncer.
La secuenciación masiva es una herramienta útil para estudiar el miRNAoma en tumores
sólidos, por lo que utilizamos secuenciación de alto rendimiento (NGS), para estudiar la
expresión de miRNAs en una cohorte de pacientes con CPNM en estadios tempranos (tejido
pulmonar tumoral vs normal).
Materiales y métodos: Se secuenciaron por NGS (plataforma SOLiD) en multiplex muestras
de RNA de 35 pacientes (tejido tumoral y normal) con un RIN ≥ 8, enriquecidas en la
fracción de miRNAs. Los datos fueron normalizados y las secuencias se compararon con
bases de datos de miRNAs maduros y no maduros. Para el análisis funcional se usaron las
bases de datos, Gene Ontology (GO) y KEGG.
Resultados: La secuenciación usando marcaje de códigos de barras multiplexado, de 35
muestras de miRNAs pareadas (tumor vs tejido normal) resultó en un total de 1268 miRNAs
(maduros y no maduros) detectados en al menos una muestra. Se encontraron 33 miRNAs
sobreexpresados y 17 infraexpresados de manera significativa en las muestras tumorales
frente a parénquima pulmonar normal. El análisis funcional reveló diferencias significativas
en 7 vías KEGG y en 400 procesos biológicos (PB) de acuerdo con GO. Al comparar las histología
adenocarcinoma vs escamosa hubo diferencias significativas en 19 vías KEGG y 144
PB algunos de ellos relacionados con la angiogénesis y regulación de VEGF.
Conclusiones: La técnica utilizada para la expresión diferencial de miRNAs es una tecnología
útil y novedosa para la caracterización del miRNAome. El uso de códigos de barras
multiplexado permite reducir el coste por muestra. Varios miRNAs fueron expresados diferencialmente
entre tejido tumoral frente al normal. Los ensayos de validación están en
proceso.
P-27
ISOLATION AND CHARACTERISATION OF RHABDOMYOSARCOMA-INITIA-
TING CELLS
ALMAZÁN-MOGA A 1 , ROMA J 1 , MOLIST C 1 , REVENTÓS J 2 , SÁNCHEZ DE TOLEDO J 1 , GALLEGO S 1
1
PEDIATRIC ONCOLOGY AND HEMATOLOGY UNIT, HOSPITAL UNIVERSITARI VALL D’HEBRON, UNIVER
SITAT AUTÒNOMA DE BARCELONA, BARCELONA (RD06/0020/1021)
2
RESEARCH UNIT IN BIOMEDICINE AND TRANSLATIONAL AND PAEDIATRIC ONCOLOGY, VALL
D’HEBRON INSTITUT DE RECERCA (VHIR), UNIVERSITAT AUTÒNOMA DE BARCELONA, BARCELONA
(RD06/0020/0058)
Background: Rhabdomyosarcoma (RMS) is a malignant tumour originating from skeletal
muscle myoblastic precursors. Current treatment protocols yield overall survival of 60-65%.
Recently, growing evidence supporting the existence of tumour-initiating cells (TICs) in a
wide range of cancers has been accumulated. These cells are thought to be the only cells
able to initiate primary tumours, produce metastases and survive conventional therapies.
Recent publications have suggested that RMS follows the cancer stem cell model. For this
reason, the design of therapies specifically targeting this subpopulation, in a primary tumour
or in blood circulating tumour cells, may considerably reduce the probability of metastases
and relapses in RMS patients.
Objectives: To isolate and molecularly characterise the TICs subpopulation in RMS cell
lines, primary tumours and circulating RMS cells to achieve a significant pharmacological
inhibition of the most significant signalling pathways for TIC maintenance.
Methods: Spheres and holoclone assays were used to enrich and isolate TICs in RMS
cell lines. Real-time PCR and Western blot were used to determine activated signalling
pathways in this subpopulation. Gamma-secretase inhibitors (DAPT and GSI XXI) and Vismodegib
were used to inhibit Notch and Hedgehog pathways, respectively.
Results: RMS cell lines formed spheres and holoclones which showed an upregulation of
Notch and Hedgehog pathways. Pharmacological inhibition of both pathways reduced the
ability of RMS cell lines to form spheres and holoclones, which suggests that these pathways
play an important role in the maintenance of putative RMS-initiating cells.
Conclusions: Our in vitro results point to Notch and Hedgehog pathways as therapeutic
targets against RMS-initiating cells, thereby indicating that their pharmacological inhibitors
may improve RMS patients survival, especially in high-risk and recurrent cases.
70 71

P-28
EFFECTS OF GAMMA-SECRETASE INHIBITORS IN RHABDOMYOSARCOMA
MOUSE MODELS
MOLIST C 1 , ALMAZÁN-MOGA A 1 , ROMA J 1 , GARCIA M 2 , DOLL A 2 , REVENTÓS J 2 , SÁNCHEZ DE
TOLEDO J 1 , GALLEGO S 1
1
PEDIATRIC ONCOLOGY AND HEMATOLOGY UNIT, HOSPITAL UNIVERSITARI VALL D’HEBRON, UNIVER
SITAT AUTÒNOMA DE BARCELONA, BARCELONA (RD06/0020/1021)
2
RESEARCH UNIT IN BIOMEDICINE AND TRANSLATIONAL AND PAEDIATRIC ONCOLOGY, VALL
D’HEBRON INSTITUT DE RECERCA (VHIR), UNIVERSITAT AUTÒNOMA DE BARCELONA, BARCELONA
(RD06/0020/0058)
Background: Rhabdomyosarcoma (RMS) is a malignant tumour derived from myoblastic
precursors of skeletal muscle. It is a rare disease with an incidence of 5.3 cases/million/
year affecting mainly children under 15 years old. Current treatments include chemotherapy,
surgeryand radiotherapy, with 5-year overall survival of 60-65%. Our previous in vitro
studies suggest that inhibition of the NOTCH pathway bygamma-secretase inhibitors produces
a significant decrease in invasiveness of RMS cell lines in culture. Moreover, NOTCH
pathway activation seems to play a crucial role in the activation of the N-Cadherin.
Objectives: To establish the animal models and to ascertain theeffects of NOTCH pathway
inhibition using murine xenograft models of RMS in an attempt to find new molecular targets
for treatingpatients with RMS.
Methods: Intramuscular and intravenous injection of RH-30 RMS cells into SCID mice and
treatment with NOTCHpathway inhibitors.
Results: Primary RMS tumours showed a reduction in size when treated with the gammasecretase
inhibitor DAPT.Currently, the model of metastasis (by intravenous injection of
RH-30 RMS cells) is under development.
Discussion: The characterization of the NOTCH pathway in RMS murine xenografts in
combination with the use of NOTCH pathway inhibitors may lead to noveltherapeutic strategies
for children with high risk or recurrent rhabdomyosarcoma. We hypothesize that
the use of specific NOTCH pathwayinhibitors in vivo, in a xenograft mouse model of RMS,
could lead to new co-adjuvant treatments for patients with metastatic disease orhigh risk
of developing metastasis.
P-29
MOLECULAR EVENTS IN ENDOMETRIAL CARCINOSARCOMAS AND THE
ROLE OF HMGA2 IN ENDOMETRIAL CARCINOGENESIS
ROMERO-PÉREZ L 1 , CASTILLA MA 1 , DÍAZ-MARTÍN J 1 , MORENO-BUENO G 2 , PALACIOS CALVO J 3
1
INSTITUTO DE BIOMEDICINA DE SEVILLA (IBIS), SEVILLA (RD06/0020/0013)
2
INSTITUTO DE INVESTIGACIONES BIOMÉDICAS “ALBERTO SOLS”-UAM ”/ FUND.MD ANDERSON
CANCER CENTRE, MADRID
3
HHUU VIRGEN DEL ROCÍO-IBIS/ HHUU RAMÓN Y CAJAL, MADRID (RD06/0020/0013)
The molecular events implicated in the development of endometrial carcinosarcoma (ECS)
remain poorly understood. Using cDNA microarrays, we analyzed a group of 15 ECSs and
compared their gene expression profiles with those obtained from a group of 23endometrioid
endometrial carcinomas (EECs).
We demonstrated changes in the expression of genes modulating processes such as the
epithelial-mesenchymal transition (EMT), muscle differentiation, the expression of cancer/
testis antigens (CTAs) and immune response in ECSs.
The HMGA2 gene (High Mobility Group AT-hook 2) is an embryonic nuclear factor that
mediates EMT in various tumor models and it was among the genes overexpressed in
ECSs. HMGA2 overexpression was confirmed in 54% of ECSs by qRT-PCR and immunohistochemistry.
Moreover, we found a significant inverse correlation between the expression
of HMGA2 and let-7b, a member ofthe let-7 family of miRNAs that represses HMGA2 expression.
These changes were also associated with overexpression of Lin28B, a suppressor of microRNA
biogenesis that is implicated in cancer progression and metastasis.
Finally, HMGA2 overexpression, which was detected in less than 3% of EECs, was observed
in many non-endometrioid carcinomas (NEECs) (46% of 28 samples).
This pattern of expression, restricted to NEECs and ECSs, reflects a role for HMGA2 in endometrial
carcinogenesis that is associated with aggressive phenotypes, and points to its potential
use as a marker to distinguish between endometrioid and non-endometrioid tumors.
* This study was performed in collaboration with Xavier Matias-Guiu (HHUU Arnau de Vilanova,
IRBLLEIDA, Lleida. RD06/0020/0134) and Jaime Prat (Hospital Sant Pau, Barcelona.
RD06/0020/0015)
72 73

P-30
GENETIC VARIANTS IN MIRNAS: NEW PREDICTIVE MARKERS IN THE
ORIGIN OF PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA
GUTIÉRREZ CAMINO A 1 , LÓPEZ LÓPEZ E 1 , GARCÍA-MIGUEL P 2 , SÁNCHEZ DE TOLEDO J 3 , CARBONÉ
BAÑERES A 4 , PIÑÁN MA 5 , GARCÍA DE ANDOIN N 6 , NAVAJAS A 5 , GARCÍA-ORAD A 1
1
UNIVERSIDAD DEL PAÍS VASCO, BILBAO (RD06/0020/0048)
2
HOSPITAL LA PAZ, MADRID (RD06/0020/0048)
3
HOSPITAL VALL D´HEBRÓN, BARCELONA (RD06/0020(1021)
4
HOSPITAL MIGUEL SERVET
5
HOSPITAL DE CRUCES, BILBAO (RD06/0020/0048)
6
HOSPITAL DONOSTIA, DONOSTIA (RD06/0020/0048)
Purpose: Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children.
ALL develops during early life, and consequently, a strong genetic influence is expected.
In fact, several polymorphisms (SNPs) have been associated with ALL in previous GWAS.
MicroRNAs (miRNA) are non-coding RNAs that act as negative regulators of the expression
of other genes. Up to 171 deregulated miRNAs have been reported in children with ALL,
showing its importance in the disease.
Recent studies have provided evidence that SNPs in miRNAs and in genes of the processing
machinery of miRNAs migth be associated with risk of developing cancer, like SNP
rs11614913 in mir196a2 with the risk of lung and breast cancer and rs7813 in the GEMIN4
with ovaric and bladder cancer. Nevertheless, there are no studies in ALL risk.
The aim of this study was to evaluate the role of SNPs in both precursor miRNA and genes
related to miRNA biogenesis in susceptibility to pediatric ALL.
Material and Methods: We analyzed 238 childhood B-cell ALL patients during complete
remission and 352 healthy controls. 118 SNPs in miRNAs and miRNA biogenesis pathway
were studied with Taqman OpenArray platform.
Results: Eight polymorphisms were found to have significant associations (p>0,05) with
risk of childhood ALL. Five of them were located in the TNRC6B, CNOT6, DGCR8 and RNA-
SEN genes, which are involved in miRNA biogenesis. The other 3 SNPs were located in
miR-449b, miR-612 and miR-499.
Conclusion: Our results suggest that SNPs in miRNAs and miRNA biogenesis pathway
may affect childhood ALL susceptibility.
This project was supported by RETICS (RD/06/0020/0048), UPV/EHU (UFI 11/35) Basque
Government (GIC10/71, SAI10/03 and 2006111015) Jesús de Gangoiti Barrera Foundation.
Support by SGIker (UPV/EHU) is gratefully acknowledged.
P-31
ACTIVITY OF LENALIDOMIDE IN IN VITRO AND IN VIVO MODELS OF
BORTEZOMIB-RESISTANT MANTLE CELL LYMPHOMA
MOROS A 1 , SABORIT-VILLARROYA I 1 , PEREZ-GALAN P 1 , MARTINEZ A 2 , CAMPO E 2 , COLOMER D 2 ,
ROUE G 1
1
HOSPITAL CLÍNIC-IDIBAPS (RD06/0020/0014)
2
HOSPITAL CLÍNIC-IDIBAPS (RD06/0020/0039)
Mantle cell lymphoma (MCL) is an aggressive B lymphoid neoplasm genetically characterized
by the t(11;14)(q13;q32) leading to the overexpression of cyclin D1. Despite the
promising introduction of the proteasome inhibitor bortezomib in the clinical practice, not
all the patients respond and relapse frequently occurres. When comparing the behavior of
both bortezomib-resistant and bortezomib-sensitive cell lines in a xenotransplant mouse
model, we observed an increased tumorigenecity of bortezomib-resistant, suggesting a
major capacity of these tumors to interact with lymphoid microenvironment.
We assessed the activity in vitro and in vivo of the immunomoduladory drug lenalidomide
either alone or combined with the proteasome inhibitor in both bortezomib-resistant and
bortezomib-sensitive samples. Lenalidomide single agent was found to exert modest antitumoral
activity in 3/10 MCL cell lines, corresponding to those cells with either primary or
acquired resistance to the proteasome inhibitor.
Conversely, mice bearing bortezomib-resistant tumors and treated for 3 weeks with a 10-50
mg/kg/day regimen of lenalidomide, showed a 30 to 45% reduction in tumor burden when
compared to vehicle-treated group (p

P-32
VALOR PRONÓSTICO DE LA EXPRESIÓN DEL RECEPTOR CANNABINOIDE
TIPO 2, CB2, EN CÁNCER COLORRECTAL HUMANO
MARTÍNEZ-MARTÍNEZ E 1 , GÓMEZ I 1 , MARTÍN P 2 , ROMÁN L 3 , GARCÍA JM 1
1
SERVICIO DE ONCOLOGÍA MÉDICA, HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-MAJADAHONDA,
MADRID (RD06/0020/0020)
2
UNIDAD DE PATOLOGÍA MOLECULAR DEL CÁNCER, HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-
MAJADAHONDA, MADRID (RD06/0020/0047)
3
UNIDAD DE NEUROINMUNOLOGÍA, HOSPITAL UNIVERSITARIO PUERTA DE HIERRO-MAJADAHONDA,
MADRID
El receptor cannabinoide tipo 2 (CB2), es uno de los receptores implicados en la señalización
mediada por (endo)cannabinoides, y cuya actividad no se asocia a efectos psicotrópicos.
Se localiza principalmente en células del sistema inmune y tejidos periféricos, y su
sobre-expresión ha sido descrita en determinados tipos de cáncer, entre ellos cáncer de
colon. Actualmente hay un debate activo sobre su potencial como diana terapéutica, sin
embargo no existen trabajos acerca de su implicación en la progresión de la enfermedad en
series de tumores colorrectales humanos.
El estudio se ha realizado en muestras de tumores colorrectales de 175 pacientes donde
CB2 se ha detectado en un 28.6% de los casos mediante RT-PCR. CB2 se detecta mayoritariamente
en las células epiteliales del tumor, siendo rara y menos intensa en células
epiteliales normales (análisis inmunohistoquímico). CB2 se expresa en tumores con baja
expresión de FAAH (RT-PCR), enzima que degrada los endocannabinoides, y con una elevada
tasa de proliferación, como han demostrado los análisis inmunohistoquímicos de CB2
y Ki67. La expresión de CB2 se correlaciona con ganglios afectados p=0,016, parámetro
establecido de mal pronóstico. Finalmente, la expresión de CB2 en las muestras tumorales
se asocia tanto a una peor supervivencia libre de enfermedad, p=0.014, como a una peor
supervivencia global, p

P-34
CARACTERIZACIÓN CLÍNICA Y BIOLÓGICA DEL LINFOMA DE LA ZONA
MARGINAL ESPLÉNICO CON Y SIN LINFOCITOS VELLOSOS CIRCULANTES
CALULL A 1 , SALIDO M 1 , BELLOSILLO B 1 , SOLÉ F 1 , FLORENSA L 1 , FERRE A 1
1
HOSPITAL DEL MAR, PARC DE SALUT MAR BARCELONA (RD07/0020/2004)
Fundamentos: El linfoma esplénico de células B pequeñas con infiltración difusa de la
pulpa roja (LEDPR) es una entidad provisional de la OMS distinta del linfoma de la zona
marginal esplénico (LZME) convencional. El LEDPR presenta diferencias clínico-biológicas
respecto al LZME: infiltración difusa de la pulpa roja esplénica, ausencia de alteraciones
citogenéticas por técnicas convencionales, hipermutaciones de IGHV en el 80% de casos
y uso selectivo de VH3-23 y VH4-34. El diagnóstico del LEDPR se basa en la histología
esplénica pero ello frecuentemente no es factible. Dado que el LEDPR se caracteriza por
la presencia en sangre periférica (SP) de numerosos linfocitos vellosos, el objetivo del estudio
fue analizar la existencia de diferencias entre los LZME con (LZMEv.) y sin linfocitos
vellosos circulantes (LZME no v.) que apoyen la consideración del LEDPR como una entidad
distinta. Pacientes y métodos: Se estudiaron muestras de SP de 38 pacientes (LZMEv., 18;
LZME no v., 18; LEDPR, 2), considerando LZMEv. los casos con >25% de linfocitos vellosos.
Se analizaron las características morfológicas, fenotípicas, citogenéticas, SNPa (Genome-
WideHuman SNP Array 6.0, Affymetrix), moleculares (estado mutacional de IGHV y genes
VH) y la posible asociación de los diferentes datos clínicos y biológicos.
Resultados: Las principales características clínico biológicas se detallan en la tabla. El
estudio de SNPa mostró heterogeneidad de las alteraciones cromosómicas, ausencia de
alteraciones recurrentes y una mayor inestabilidad genómica en los LZME no v. Los grupos
LZMEv. y LZME no v. mostraron diferencias en el tipo de cadena ligera de superficie expresada
(P=0,041) y en la distribución de frecuencias de cariotipos normales (P=0,086) y
complejos (P=0,008)
Conclusiones: Son necesarios estudios con un mayor número de casos para determinar
si la presencia de linfocitos vellosos en SP en pacientes con LZME puede ser considerada
como sugestiva de corresponder a una entidad distinta al LZME sin linfocitos vellosos.
78 79

P-35
ROLE OF AhR IN MURINE SPERMATOGENESIS THROUGH REGULATION OF
THE SINE B1-X35S RETROTRANSPOSON
MORENO MARÍN N* 1 , GONZÁLEZ RICO FJ* 1 , RICO-LEO EM* 1 , FERNÁNDEZ SALGUERO PM 1
1
UNIVERSIDAD DE EXTREMADURA, BADAJOZ (RD06/0020/1016)
*THESE AUTHORS CONTRIBUTED EQUALLY TO THIS PROJECT AND SHOULD BE CONSIDERED CO-FIRST
AUTHORS
The dioxin receptor AhR is a transcription factor highly conserved. Recent studies have
shown that AhR has an important role in cell and organ homeostasis, besides its well known
implication in toxicity.
We have also reported that AhR cooperates with the EMT regulator factor Slug in the activation
of the novel murine B1-X35S retrotransposon, which has an insulator/boundary activity
able to repress gene expression. The alterations in processing of retrotransposon-derived
transcripts are considered a very relevant mechanism in disease progression, particularly in
cancer. In mammals, methylation is the main transposable elements (TEs) silencing mechanism.
This DNA methylation is temporarily lost in male germ cells, being the piRNA pathway
the main defense against transposons. Those piRNAs are produced in a dense perinuclear
cloud-like region called Nuage, where they associate with MILI and MIWI (murine orthologs
of PIWI proteins) to form an active piRNA-induced silencing complex.
On the other hand, previous studies showed that AhR is involved in germ cells maturation
and fertility. In this study, we have used mouse testis AhR+/+ and AhR-/-, at different
stages of spermatogenesis. We have seen that mice AhR-/- show a deregulation in the
B1X35S/piRNAs balance. Thus, these animals displayed a higher B1X35S mRNA expression
compared to wild type ones.
Furthermore, we determined small RNA expression by radioactive SDS-PAGE and found that
piRNAs were increased in AhR-/-, and individual RNA bands that were detected by Northern
Blot assays were absent in AhR+/+. We have also found differences in MILI, MIWI and
MVH (another Nuage component) expression by both qPCR and WB assays. Moreover, we
observed relocation towards the more differentiated areas of the seminiferous tubules in all
of three proteins in the KO phenotype.
P-36
DIETARY IRON, HEME IRON AND BODY IRON STATUS AND CANCER RISK
– A SYSTEMATIC REVIEW
FONSECA NUNES A 1 , JAKSZYN P 1 , AGUDO A 1
1
INSTITUTO CATALÁN DE ONCOLOGÍA (ICO)-IDIBELL, BARCELONA (RD06/0020/0091)
Background: Iron has been suggested as a risk factor for different types of cancer due to
its pro-oxidant activity which can lead to more oxidative stress and DNA damage.
Objetive: To systematically review and analyze the link between iron intake and body iron
status and the risk of developing cancer.
Methods: In this article we analyzed 34 epidemiological studies that responded to our
specific search criteria using the MEDLINE database between 1995 and 2012. These criteria
included articles with information on dietary iron, total iron, heme iron, body iron status,
and cancer risk.
Results: From the 34 articles identified, 23 were prospective and 11 were case-control studies.
Many of these studies (18 studies) referred to gastro-intestinal tract cancer (esophageal,
gastric, and colorectal), eight related to breast and four to lung cancer. The rest
investigated other cancers (endometrial, pancreatic, prostate and bladder). All studies took
into account the dietary intake of iron and only five of them also conducted biomarkers
analysis. From the 24 studies that reported results on heme iron intake and cancer risk, 14
found a positive association (nine statistically significant). From the 19 studies that reported
data on dietary iron, the results were inconclusive. Regarding iron biomarkers studies, the
major part focused on colorectal cancer and provided mixed results.
Conclusion: Despite the heterogeneity of the results obtained in this review, there is some
tendency towards the association between heme iron intake and cancer risk. Moreover,
data on iron biomarkers was insufficient. For this reason, more studies combining research
on iron biomarkers, dietary iron intake and genetic information need to be conducted to
better understand the role of iron in cancer development.
Molecular beacons in situ techniques will be used to address possible co-localization between
these proteins and transcripts derived from B1X35S and piRNAs.
80 81

P-37
IDENTIFICATION OF PROTEIN BIOMARKERS TO IMPROVE EARLY
DIAGNOSIS IN ENDOMETRIAL CANCER
MARTÍNEZ GARCÍA E 1 , MONGE M 1 , CAMPOY I 1 , DEVIS JAUREGUI L 1 , GARCÍA A 1 , CASTELLVÍ J 1 ,
CABRERA S 1 , GIL-MORENO A 1 , CANALS F 1 , ABAL M 2 , REVENTÓS J 1 , COLÁS E 1
1
HOSPITAL VALL D´HEBRÓN, BARCELONA (RD06/0020/0058)
2
CHUS, SANTIAGO DE COMPOSTELA
Introduction and aim: Endometrial cancer (EC) is the most frequent cancer of the female
genital tract and the forth most common cancer in women in western countries. Currently,
we are in a scenario in which 20% of patients are diagnosed with advanced EC, correlating
with poor prognosis. The aim of this work is to provide a protein-non-invasive diagnostic
tool to improve early diagnosis of EC by using the uterine aspirates as an attractive proximal
body-fluid to identify biomarkers.
Methods: In the discovery phase, we performed 3 independent experiments using 2D-
DIGE and MALDI-TOF-MS proteomic technologies comparing normal endometrium versus
EC tissue. In two of the experiments, normal and tumor paired samples from 13 patients
were compared, while in the third experiment, 3 normal and 6 tumor samples from different
patients were used. Differential proteins from each experiment that fulfilled the selection
criteria of fold -1.3 > x

P-39
NOVEL IDENTIFICATION OF EXOSOMES IN UTERINE ASPIRATES AND ITS
UTILITY AS A SOURCE FOR NEW BIOMARKERS
CAMPOY I 1 , MARTÍNEZ GARCÍA E 1 , DEVIS JAUREGUI L 1 , GARCÍA A 1 , CASTELLVÍ J 1 , CABRERA S 1 ,
GIL-MORENO A 1 , ABAL M 2 , REVENTÓS J 1 , COLÁS E 1
1
HOSPITAL VALL D´HEBRÓN, BARCELONA (RD06/0020/0058)
2
CHUS, SANTIAGO DE COMPOSTELA
Background and aim: Exosomes are 40-100 nm extracellular vesicles released from a
variety of cell types. Our aim is to use exosomes as a source to identify new sensitive and
specific biomarkers for the detection of endometrial cancer through a non-invasive method,
isolating them from the uterine aspirate, which is the nearest and the easiest-to-access
body fluid in contact with the endometrium. To date, reports on exosomes coming from
uterine aspirates remain undescribed.
Methods: We standardized the protocol for the isolation of exosomes (both from uterine
aspirates and from media of cancer cell lines in culture) by ultracentrifugation-based techniques;
we characterized them by electron microscopy and immunoblot. We performed a
pilot study by LC-MS/MS isolating, quantifying, digesting and analyzing its protein fraction.
Computational analysis was performed by using Ingenuity Pathways Analysis.
Results: Membrane-vesicles were observed in uterine aspirates by electronic microscopy
by negative staining. Also, western blot analysis of the isolated exosomes revealed the presence
of known exosome markers, such as CD81, TSG-101 and other membrane proteins,
such as Annexin 2, both in uterine aspirates and cultured cell lines. LC-MS/MS analysis
enabled the identification of 153 proteins in the uterine aspirate exosomes. From the list of
proteins identified, we recognized several proteins that belong to the exosome biogenesis
and also endometrial cancer related proteins. IPA analysis identified Cellular Movement,
Immune Cell Trafficking, Cell-To-Cell Signaling and Interaction as the top networks, Cancer
as the top disease by Bio Function classification and Cell-To-Cell Signaling and Interaction
as the top Molecular and Cellular Function.
Conclusion: Our data demonstrates that the identification of the protein content of exosomes
isolated from uterine fluids is feasible and promising for the identification of critical
molecules involved in endometrial cancer, which can be used as diagnostic markers.
P-40
INHIBITORY MECHANISMS OF THE RESPONSE TO TGF-B BY THE THYROID
HORMONE RECEPTORS
ALONSO MERINO E 1 , MARTIN OROZCO R 1 , RUIZ LLORENTE L 1 , FANJUL RODRIGUEZ LF 1 , MARTI-
NEZ IGLESIAS O 1 , ARANDA IRIARTE A 1
1
INSTITUTO DE INVESTIGACIONES BIOMÉDICAS “ALBERTO SOLS”, MADRID (RD06/0020/0036)
The thyroid hormone receptors, encoded by the TRα and TRβ genes, are ligand-dependent
transcription factors that belong to the nuclear receptor superfamily, being the 3,5,3’-triiodothyronine
(T3) their main ligand. In addition to the role of these receptors in growth,
development and metabolism, there is increasing evidence that they can also inhibit transformation
and act as tumor suppressors.
We now have analysed the possibility that TRs could block responses to the transforming
growth factor beta (TGFβ). This regulatory cytokine exerts tumor-suppressive effects in
normal cells, but on the other hand, cancer cells evade this repression and TGFβ can promote
some tumorogenic processes such as cell proliferation, cell invasion, immune regulation
and microenvironmet modification.
In this work we demonstrate that TR, activated by T3 binding, can block transactivation
by TGFβ of reporter plasmids containing a Smad Binding Element (SBE) and repress transcription
of endogenous TGFβ target genes. We have also demonstrated that transfection
of Smad transcription factors stimulate the activity of the reporter plasmid in the absence
of TGFβ, and that T3 inhibits this activation. In immunofluorescence assays we have seen
that reversion of the TGFβ response is not mainly due to inhibition of Smads translocation
to the nucleus. However, in chromatin immunoprecripitation assays (ChIP), we have observed
that T3 inhibits TGFβ–dependent recruitment of Smads to target genes promoters
containing SBEs.
In addition, T3 reduces acetylated histones and increases histone decetylase 3 (HDAC3)
recruitment to TGFβ target genes. The hormone is also able to block TGFβ-dependent
proliferation and migration. These results demonstrate that T3 blocks transcriptional responses
to TGFβ, and suggest that some of the anti-tumorigenic and anti-invasive actions of
the thyroid hormone receptors can involve repression of the activity of the TGFβ signalling
pathway.
84 85

P-41
LA FOSFORILACIÓN DE eIF4E AUMENTA LA SUPERVIVENCIA Y EL CRECI-
MIENTO CELULAR BAJO SITUACIONES DE ESTRÉS
MARTINEZ A 1 , SESE M 1 , HERNANDEZ J 1 , SANSANO I 1 , PEG V 1 , AASEN T 1 , RAMÓN Y CAJAL S 1
1
Institut Recerca Vall Hebrón (VHIR), Barcelona (RD06/0020/0104)
The SOX11 gene encodes a member of the SOX (SRY-related HMG-box) family of transcription
factors involved in the regulation of embryonic development and in the determination
of the cell fate.
El control de la traducción proteica juega un papel importante en el desarrollo y progresión
tumoral. Un factor clave es eIF4E, altos niveles de su forma fosforilada se han descrito en
un gran número de tumores. eIF4E media la asociación del complejo eIF4F con la estructura
5’cap del mRNA y es esencial para la traducción proteica. Contribuye al transporte de
ciertos mRNAs hacia citoplasma y es un componente de gránulos de estrés y processing
bodies. Por datos preliminares in vitro y en series clínicas, se evaluó el papel de la fosforilación
de dicha proteína en relación con proliferación y resistencia a diversos tipos de estrés
celular.
Líneas celulares de carcinoma de mama (MDA-MB231, MDA MB-468) y una línea celular
de queratinocitos (HaCaT) se infectaron con retrovirus que expresaban la forma salvaje,
hipofosforilada (S209A) y fosfomimética (S209D) de eIF4E. Las células fueron sometidas a
diferentes tipos de estrés: oxidativo, deprivación de nutrientes, cisplatino y diversos inhibidores
de la transcripción.
Tras el estrés se observó una recuperación mayor en todas las líneas celulares que expresaban
eIF4E-S209D, dicha resistencia se asoció a un aumento de la expresión de varias
proteínas que contienen elementos ARE (ciclinaD1, b-catenina, 4E-T, Mcl-1 y Cx43). Dicho
incremento se observó también tras tratamiento concomitante con actinomicina-D. En situación
basal, observamos una colocalización de eIF4E-S209D y 4E-T en cuerpos citoplasmáticos.
Estos complejos colocalizan con Ago2 pero no con marcadores de gránulos de
estrés (TIA-1) y processing bodies (DCP1A). Por co-immunopreciptacion, observamos que
peIF4E interactúa con 4E-T, Ago2 y Hur.
La fosforilación de eIF4E confiere resistencia a diversos tipos de estrés celular. El aumento
de ciertas proteínas sugiere que la fosforilación de eIF4E y los complejos con 4E-T pueden
favorecer la acumulación y traducción más selectiva de RNAs implicados en apoptosis y proliferación
celular. Proponemos que la inhibición selectiva de la fosforilación de eIF4E puede
ser un tratamiento complementario para aumentar la respuesta a agentes antitumorales.
P-42
EXPRESIÓN DE GENES INMUNOREGULADORES EN CÁNCER DE PULMÓN
NO MICROCÍTICO
ALMAGRO LARROSA A 1 , SIRERA PÉREZ R 1 , JANTUS LEWINTRE E 1 , USÓ MARCO M 1 , LU
CAS R 1 , CAMPS HERRERO C 1
1
HOSPITAL GENERAL UNIVERSITARIO DE VALENCIA, VALENCIA (RD06/0020/1024)
En el cáncer de pulmón no microcítico (CPNM) resulta de vital importancia desarrollar biomarcadores
que nos permitan asignar un pronóstico más exacto a los pacientes en estadios
tempranos, de modo que se pueda aplicar el tratamiento adecuado en el tiempo preciso,
evitando que el cáncer se desarrolle hasta las fases tardías cuando el grado de curación es
prácticamente nulo.
En este trabajo se ha seleccionado un conjunto de 9 genes relacionados con procesos
de inmunoregulación e inflamación para analizar su expresión relativa a nivel de mRNA
mediante qPCR en muestras de tejido pulmonar de pacientes con CPNM en estadios resecables.
Los genes CCL2 y CD1c mostraron una expresión sensiblemente inferior en tejido
tumoral frente a tejido sano.
Tras ello se analizó la posible correlación de los niveles de expresión de dichos genes con
las variables clínico-patológicas más relevantes de los pacientes. Los tumores pobremente
diferenciados presentaron niveles de expresión superiores de CD209, CCL2, LGALS1 y
LGALS2; mientras que en pacientes fumadores se documentó un aumento de la expresión
de la galectina LGALS1.
Por último, se realizaron análisis de supervivencia mediante el método de Kaplan-Meier para
evaluar la utilidad de los genes como biomarcadores pronóstico en esta patología. En el
subgrupo de pacientes con histología epidermoide, aquellos con menores niveles de expresión
de CCL22 presentaron de manera significativa un aumento en la supervivencia global
(SG) y libre de progresión (TLP). En nuestra cohorte de pacientes con CPNM resecable, los
análisis de supervivencia revelaron que los niveles elevados de la galectina LGALS2 y la
quimiocina CCL2 se relacionan con un mejor pronóstico, tanto en TLP como en SG.
En resumen, los datos obtenidos en nuestro estudio aportan una nueva evidencia sobre la
necesidad de los tumores de manipular el microambiente que los rodea como paso previo
para progresar e invadir nuevos tejidos.
86 87

P-43
ESTUDIO DE CAMBIOS FOCALES EN EL NÚMERO DE COPIAS DE DNA EN
NEUROBLASTOMA MEDIANTE ARRAYS DE SNP
BERBEGALL BELTRÁN AP 1 , VILLAMÓN RIBATE E 1 , TADEO CERVERA I 2 , MARTA PIQUERAS 1 , NAVA-
RRO FOS S 1 , NOGUERA SALVÁ R 1
1
FACULTAD DE MEDICINA –UNIVERSIDAD DE VALENCIA, VALENCIA (RD06/0020/0102)
2
FUNDACIÓN DE INVESTIGACIÓN DEL HOSPITAL CLÍNICO DE VALENCIA, VALENCIA (RD06/0020/0102)
Introducción: El neuroblastoma (NB) es el tumor sólido extracraneal más frecuente en
la infancia. Genéticamente es frecuente observar cambios numéricos cromosómicos completos
(NCA) y grandes alteraciones cromosómicas segmentarias (SCA). La importancia
pronóstica de estos cambios no ha facilitado el estudio de las SCA focales (≤ 2 Mb).
Material y Métodos: Hemos analizado 145 NBs mediante arrays de SNP (Affymetrix 250K
y/o Illumina 300K). Junto con la descripción de los perfiles pangenómicos típicos (NCA y
SCA) realizamos un estudio preliminar sobre la presencia y tipo de ganancias, amplificaciones
y/o pérdidas cromosómicas focales.
Resultados: En todos los tumores analizados observamos algún tipo de alteración cromosómica.
Un perfil de NCA estaba presente en el 5.6% de los casos. El 72.4% de los casos
presentaron un perfil de grandes SCA, estando combinadas en un 90% de ellos con SCA
focales. En el 4.8% de los casos únicamente detectamos SCA focales. Se observaron tanto
ganancias (48%), amplificaciones (13%) como deleciones (39%) focales. Se encontraron
una media de tres (1-9) SCA focales por caso. Los perfiles pangenómicos de un 17.2% de
los casos presentaron cromosomas no evaluables y por tanto considerados incompletos.
Conclusiones: La alta frecuencia de SCA focales detectada en nuestro estudio y no consideradas
hasta el momento actual implica la necesidad de conocer su impacto pronóstico y
su relación con otros factores de valor pronóstico reconocido.
Financiación: ISCIII (RD06/0020/0102 y PI00015) y FAEC (396/2009).
P-44
MicroRNAs IN URINE AS BIOMARKERS FOR PROSTATE CANCER
MONTES M 1 , OLIVAN M 1 , SEQUEIROS T 1 , GARCIA M 1 , RIGAU M 1 , MOROTE J 1 , REVENTÓS J 1 ,
AND DOLL A 1
1
VALL D’HEBRON RESEARCH INSTITUTE (VHIR) AND UNIVERSITY HOSPITAL, BIOMEDICAL RESEARCH
UNIT, BARCELONA, (RD06/0020/0058)
Background and aims: Prostate cancer (PCa) is the most common neoplasia among
males from developed countries and the second leading cause of death from cancer. During
the last years, serum prostate specific antigen (PSA) has been used as biomarker for PCa
diagnosis. Although PSA test has increased PCa detection, it has a low specificity and leads
to over diagnosis and over treatment, therefore, it is necessary to improve the current diagnostic
methods for PCa. In the past decade, urine has received more and more attention for
its simplicity, as well as its potential use in identifying new biomarkers as non- or minimum
invasive detection method. Deregulation of microRNAs (miRNAs) in serum/plasma or tissue
has been associated with many diseases including PCa, suggesting the possible use of
miRNAs as diagnostic biomarkers also in other body fluids. For that reason the aim of this
study was to evaluate if miRNAs known to be deregulated in blood or tissue could also be
detected in urine and used as biomarkers for the detection of PCa.
Methods: Post-prostate massage urine samples were prospectively collected from 40 consecutive
patients, who will undergo a prostatic biopsy as part of their routine medical care,
due to the suspicion of PCa (PSA≥4.0 ng/mL and/or abnormal digital rectal examination).
Total RNA was isolated of 20 PCa patients and 20 benign controls and differential expression
levels of 21 selected miRNAs were analyzed by RT-qPCR.
Results: Data showed that a total of 7 miRNAs were differentially expressed, 5 of them
were down- and 2 up-regulated significantly in the urine of PCa patients compared with the
controls (p

P-45
METHODS FOR RNA AND miRNA PURIFICATION IN EXOSOMES FROM
URINE OF PROSTATE CANCER PATIENTS
OLIVAN M 1 *, RIGAU M 1 *, MONTES M 1 , SEQUEIROS T 1 , ALTADILL T 2 , GARCIA M 1 VIEGAS
M 2 , REVENTÓS J 1 , DOLL A 1
1
BIOMEDICAL RESEARCH UNIT, RESEARCH INSTITUTE, VALL D’HEBRON UNIVERSITY HOSPITAL,
BARCELONA (RD06/0020/0058)
2
TRANSBIOMED S.L. PARC CIENTÍFIC DE BARCELONA
* EQUALLY CONTRIBUTING
Urine has become one of the most attractive biofluids in biomedical research. Urinary exosomes
have been recently described as carriers of genetic information and a potential
source of new cancer biomarkers, specifically for prostate cancer (PCa). Analysing the
transcriptome in secreted PCa exosomes in urine has the advantages of being both noninvasive
and informative as to the overall tumor malignancy status, including tumor mRNA
and miRNA levels to be used for PCa diagnosis.
Biomarker discovery approaches in urine have been hindered by concerns for reproducibility
and inadequate standardization of protocols. Reproducible procedures for the preparation
of RNA and miRNA samples isolated from urinary exosomes are essential for meaningful
transcriptomic analyses.
Here we tried to optimize RNA and miRNA extraction from urinary exosomes. In order to
evaluate the efficacy of purification we performed RTqPCR for different housekeeping genes
and miRNAs.
Our results show that urinary exosomes serve as excellent reservoir for nucleic acids, as
they maintained stable along the time, and therefore can be suitable for PCa biomarker
discovery.
P-46
P95HER2/90-100kDa INDUCED SIGNALING LEADS TO APOPTOSIS ELUCI-
DATING A POSSIBLE MOLECULAR SWITCH BETWEEN OIS AND APOPTOSIS
BERNADÓ MORALES C 1 , ARRIBAS J 1
1
VALL D’HEBRÓN INSTITUT D’ONCOLOGIA (VHIO), BARCELONA (RD06/0020/0022)
HER2, an ErbB family tyrosine kinase receptor, is overexpressed in 15%-25% of breast
cancer tumors and its overexpression correlates with the severity of the malignancy. A
subtype of HER2-positive tumors of particularly poor clinical outcome expresses, in addition
to full-length HER2, a heterogeneous series of HER2 c-terminal fragments (CTFs), collectively
known as p95HER2. So far, only membrane bound fragments have been shown to be
active: the p95HER2/90-100kDa, generated by proteolytic cleavage, and the p95HER2/100-
115kDa, generated by alternative initiation of translation. Expression of p95HER2/100-
115kDa leads cells to senescence, an essentially irreversible cell cycle arrest, contributing to
tumor growth and metastasis formation by secreting many pro-tumoral and pro-metastatic
factors.
In this work we address the functional characterization and the mechanism of activation of
p95HER2/90-100kDa concluding thatp95HER2/90-100kDa, unlike HER2 and the previously
characterized p95HER2/100-115kDa, is not able to signal in an autonomous manner in cells
expressing low levels of other HER receptors. In fact, we show that p95HER2/90-100kDa is
activated upon heterodimerization with HER3.
Functionally, expression of p95HER2/90-100kDa, although being very similar to
p95HER2/100-115kDa, leads to cell death. Analysis of different apoptosis markers has
shown that the expression of the p95HER2/90-100kDa induces apoptosis, and only a few
fraction of the cells enter in senescence. Although both senescence and apoptosis restrain
tumor growth, senescent but not apoptotic cells may contribute to tumor invasion. Therefore,
the unexpected different outcome between the two p95HER2 active forms provides us a
useful tool to define a possible switch between apoptosis and senescence.
90 91

Apellidos Nombre E-mail Grupo RTICC Centro
Apellidos Nombre E-mail Grupo RTICC Centro
Aasen
Trond trond.aasen@vhir.org RD06/0020/0104 Institut Recerca Vall Hebron (VHIR)
Fabregat Romero Isabel ifabregat@idibell.cat
Adema
Vera
vadema@carrerasresearch.org RD07/0020/2004 INSTITUT DE RECERCA JOSEP CARRERAS
Faoro
Camilla camilla.faoro@studio.unibo.it
Ajona Martínez-Polo Daniel dajonama@unav.es
RD06/0020/0066 Centro de Investigacion Médica Aplicada
(CIMA)
Felipe García Saray saray.felipe@uv.es
Albero Gallego Robert ralbero@clinic.ub.es
RD06/0020/0039 Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
Fernández Álvarez Lara Paula lpfernandez@iib.uam.es
Almagro Larrosa
Almazan Moga
Alonso Merino
Adrián
Ana
Elvira
camps_car@gva.es
ana.almazan@vhir.org
emerino@iib.uam.es
RD06/0020/1024
RD06/0020/1021
RD06/0020/0036
Hospital General de Valencia
Institut Recerca Vall Hebron (VHIR)
Instituto de Investigaciones Biomédicas “Alberto
Sols” IIB
Fernando Peidró
Ferrer Sánchez
Fonseca Nunes
Joan
Irene
Ana Celeste
jfernando@idibell.cat
iferrer@santpau.cat
afonseca@iconcologia.net
Amador Espinosa Virginia vamador@clinic.ub.es RD06/0020/0039 Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
Gallach Garcia Sandra gallach_sangar@gva.es
Balsas Claveria
Barrasa Ardila
Patricia
Eva María
PBALSAS@clinic.ub.es
ebarrasa@unex.es
RD06/0020/0051
RD06/0020/1016
IDIBAPS
Universidad de Extremadura
Garcia López Marta marta.garcia.lopez@vhir.org
Beà Bobet Sílvia sbea@clinic.cat
RD06/0020/0039 Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
Gil Santano
Giménez Bonafé
Joan
Pepita
jgil@ub.edu
pgimenez@ub.edu
Berbegall Beltrán Ana Pilar ana.berbegall@.uv.es RD06/0020/0102 FACULTAD DE MEDICINA UNIVERSITAT DE
VALENCIA
Gonçalves Restani Rossana rgrestani@idibell.cat
Bernadó Morales
Bilbao Aldaiturriaga
Cristina
Nerea
cbernado@vhio.net
nbilbao022@ikasle.ehu.es
RD06/0020/0022
RD06/0020/0048
Instituto de Oncologia Vall d’Hebron (VHIO)
Universidad del País Vasco/Euskal Herriko Unibertsitatea
(UPV/EHU)
González Rico
Gutiérrez Camino
Francisco
Angela
fjgonzalez@unex.es
gutierrezcamino@gmail.com
Bonastre Llort Ester
ebonastre@idibell.cat RD06/0020/0062 Programa Epigenetica i Biologia del Cancer-
PEBC, Bellvitge Biomedical Research Insititute-
Hernández Losa Javier jahernan@vhebron.net
IDIBELL
Hernandez Pous Luis
hernan@clinic.ub.es
Calull Bagó
Campoy Moncayo
Anna
Irene
a.calull@gmail.com
irene.campoy@vhir.org
RD07/0020/2004
RD06/0020/0058
IMIM-Hospital del Mar, Barcelona
Institut de Recerca Hospital Universitari Vall
Herrera Tejero Alberto aherrera@idiphim.org
Hebron
Cánovas Hernández Verónica veronica.canovas@vhir.org RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
Herrera Torres Mercedes mherrera@idiphim.org
Carnicero Cáceres Silvia aivlisxii@yahoo.es
RD06/0020/0107 HOSPITAL UNIVERSITARIO MARQUÉS DE VAL-
DECILLA - IFIMAV
Jantus Lewintre
Jares Gerboles
Eloisa
Pedro
jantus_elo@gva.es
pjares@clinic.ub.es
Castellana Esteban
Catasús Cols
Bárbara
Lluís
barbara.castellan@vhir.org
lcatasus@santpau.cat
RD06/0020/0104
RD06/0020/0015
Institut Recerca Vall Hebron (VHIR)
Institut de Recerca Hospital de la Santa Creu
i Sant Pau
Jubierre Zapater
Lafita Navarro
Luz
Mª Carmen
luzjubierre@gmail.com
lafitac@unican.es
Colomer Pujol Dolors dcolomer@clinic.cat
RD06/0020/0014 Hospital Clínic- IDIBAPS
Lee Vergés Eriong elee@clinic.ub.es
Contador Troca
Cortés Lavaud
María
Xabier
mariac@unex.es
xcortes@alumni.unav.es
RD06/0020/1016
RD06/0020/0078
Universidad de Extremadura
Centro de Investigacion Médica Aplicada
Llauradó Fernández Marta marta.llaurado@vhir.org
(CIMA)
López López Elixabet elixabet.lopez@ehu.es
Cosialls Castel
Crosas Molist
Devis Jauregui
Ana Maria
Eva
Laura
anamcosialls@ub.edu
ecrosas@idibell.cat
laura.devis@vhir.org
RD06/0020/0097
RD06/0020/0097
RD06/0020/0058
IDIBELL-Universitat de Barcelona
IDIBELL-Universitat de Barcelona
Institut de Recerca Hospital Universitari Vall
Hebron
Luján Barroso
Maicas Irigaray
Leila
Miren
llujan@iconcologia.net
mmaicas@alumni.unav.es
Doll
Andreas andreas.doll@vhir.org RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
Majem Cavaller Blanca blanca.majem@vhir.org
Enjuanes Guardiola
Anna
enjuanes@clinic.ub.es
RD06/0020/0039
Institut d’Investigacions August Pi i Sunyer –
94 Mar
RD07/0020/2004
95
IDIBAPS / Hospital Clinic
Mallo
mmallo@carrerasresearch.org
RD06/0020/0097 Universitat de Barcelona- IDIBELL
RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
RD06/0020/0033 Registro Nacional de Tumores Infantiles. Universitat
de Valencia
RD06/0020/0060 Instituto de Investigaciones Biomédicas “Alberto
Sols” IIB
RD06/0020/0097 IDIBELL-Universitat de Barcelona
RD06/0020/0015 IIB Sant Pau
RD06/0020/0091 Institut d’Investigació Biomèdica de Bellvitge
(IDIBELL)
RD06/0020/1024 Hospital General de Valencia
RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
RD06/0020/0097 IDIBELL-Universitat de Barcelona
RD06/0020/0097 IDIBELL-Universitat de Barcelona
RD06/0020/0062 Programa Epigenetica i Biologia del Cancer-
PEBC, Bellvitge Biomedical Research Insititute-
IDIBELL
RD06/0020/1016 Universidad de Extremadura
RD06/0020/0048 Universidad del País Vasco/Euskal Herriko Unibertsitatea
(UPV/EHU)
RD06/0020/0104 Institut Recerca Vall Hebron (VHIR)
RD06/0020/0039 Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
RD06/0020/0020 Hospital Universitario Puerta de Hierro-Majadahonda
RD06/0020/0020 Hospital Universitario Puerta de Hierro-Majadahonda
RD06/0020/1024 Hospital General de Valencia
RD06/0020/0039 Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
RD06/0020/1021 Institut Recerca Vall Hebron (VHIR)
RD06/0020/0017 Universidad de Cantabria
RD06/0020/0014 IDIBAPS-Centre Esther Koplowitz
RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
RD06/0020/0048 Universidad del País Vasco/Euskal Herriko Unibertsitatea
(UPV/EHU)
RD06/0020/0091 Institut d’Investigació Biomèdica de Bellvitge
(IDIBELL)
RD06/0020/0078 Centro de Investigacion Médica Aplicada
(CIMA)
RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
INSTITUT DE RECERCA JOSEP CARRERAS

Apellidos Nombre E-mail Grupo RTICC Centro
Apellidos Nombre E-mail Grupo RTICC Centro
Martín Garcia David DMARTING@clinic.ub.es RD06/0020/0039 Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
Reventos
Jaume
Martín Guerrero Idoa
Idoia.marting@ehu.es RD06/0020/0048 Universidad del País Vasco/Euskal Herriko Unibertsitatea
(UPV/EHU)
Rey Barroso
Rico Leo
Javier
Eva María
MartínezBarriocanal
Martínez Díaz
Martínez Fernández
Martínez García
Águeda
Alba
Mónica
Elena
amartinez@vhio.net
amartine@ir.vhebron.net
monica.martinez@ciemat.es
elena.martinez@vhir.org
RD06/0020/0022
RD06/0020/0104
RD06/0020/0029
RD06/0020/0058
Instituto de Oncologia Vall d’Hebron (VHIO)
Institut Recerca Vall Hebron (VHIR)
CIEMAT
Institut de Recerca Hospital Universitari Vall
Hebron
Rigau Resina
Rodriguez Grijalba
Rodríguez Moreno
Marina
Vanina
Marta
Martinez Iglesias Olaia Antia omartinez@iib.uam.es RD06/0020/0036 Instituto de Investigaciones Biomédicas “Alberto
Sols” IIB
Roma Castanyer
Romero Ferraro
Josep
Octavio A.
Martínez Mañas
Martínez Martínez
Ana
Esther
anmarmaa@etsii.upv.es
esthermrt@gmail.com
RD06/0020/1024
RD06/0020/0020
Hospital General de Valencia
Hospital Universitario Puerta de Hierro-Majadahonda
Romero Pérez Laura
Martinez Soler
Matas Céspedes
Mena Varas
Fina
Alba
Maria
finamartinez@ub.edu
amatas@clinic.ub.es
mmena.1@alumni.unav.es
RD06/0020/0097
RD06/0020/0014
RD06/0020/0088
IDIBELL-Universitat de Barcelona
IDIBAPS-Centre Esther Koplowitz
Centro de Investigacion Médica Aplicada
Rosich Moya
Roué
Sagardoy Rodrigo
Laia
Gaël
Aitziber Ainara
(CIMA)
Mir Cantos
Roser rosermir83@gmail.com RD06/0020/0097 IDIBELL-Universitat de Barcelona
Saiz Ladera Cristina
Molist Muñoz
MoncunillMassaguer
Montes Pérez
Carla
Cristina
Melània
carla.molist@vhir.org
cmoncunill@idibell.cat
melania.montes@vhir.org
RD06/0020/1021
RD06/0020/0097
RD06/0020/0058
Institut Recerca Vall Hebron (VHIR)
IDIBELL-Universitat de Barcelona
Institut de Recerca Hospital Universitari Vall
Hebron
Salaverria Frigola
San Millán Blanco
Itziar
Coral
Montraveta Simón
Montuenga
Arnau
Luis
amontrav@clinic.cat
lmontuenga@unav.es
RD06/0020/0014
RD06/0020/0066
Hospital Clínic- IDIBAPS
Centro de Investigacion Médica Aplicada
(CIMA)
Sanchez Cespedes Montserrat
Morales Hernández
Morancho Armisen
Moreno Marín
Antonio
Beatriz
Nuria
antoniomh@unex.es
bmorancho@vhio.net
nuriamorenomarin@hotmail.
com
RD06/0020/1016
RD06/0020/0075
RD06/0020/1016
Universidad de Extremadura
Vall d’Hebron Institut de Oncologia (VHIO)
Universidad de Extremadura
Sánchez Pérez
Santos
Tania
Eugenio
Moreno Valle
Moros Sanz
Navarro Lopez
Miguel Angel
Alexandra
Alba
sec.rticc@usal.es
almoros@clinic.ub.es
ANAVARRL@CLINIC.UB.ES
RD06/0020/
RD06/0020/0014
RD06/0020/0039
Coordinacion RTICC
IDIBAPS-Centre Esther Koplowitz
Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
Segura Ginard
Sequeiros Fontán
Sesé Faustino
Miguel F.
Tamara
Marta
Olivan Riera Mireia mireia.olivan@vhir.org RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Solé Cañadas Carla
Hebron
Palmeri
Claudia Mariela mpalmeri@ub.edu
RD06/0020/0097 IDIBELL-Universitat de Barcelona
Sole Ristol Francesc
Palomero Gorrindo Jara
PALOMERO@clinic.ub.es RD06/0020/0039 Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
Soriano Fernández
Stanzani
Aroa
Elisabetta
Pedrola Montero Núria nuria.pedrola@vhir.org RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
Suarez-Puente Xose Anton
Peula Oliver
Pinyol Martinez
Cristina
Magda
amartine@vhir.org
mpinyolm@clinic.ub.es
RD06/0020/0104
RD06/0020/0039
Institut Recerca Vall Hebron (VHIR)
Institut d’Investigacions August Pi i Sunyer –
Tormo Martin
Tortosa I Moreno
Eduardo
Avelina
IDIBAPS / Hospital Clinic
Usó Marco Marta
Puiggros Metje
Anna
apuiggros@imim.es
RD07/0020/2004
IMIM-Hospital del Mar, Barcelona
RD06/0020/0039
96 IDIBAPS / Hospital Clinic
97
Vegliante
jaume.reventos@vhir.org RD06/0020/0058 Institut de Recerca Hospital Universitari Vall
Hebron
jarey@unex.es
evaricoleo@unex.es
marina.rigau@vhir.org
RD06/0020/1016
RD06/0020/1016
RD06/0020/0058
Universidad de Extremadura
Universidad de Extremadura
Institut de Recerca Hospital Universitari Vall
Hebron
varodrig@clinic.ub.es
martarodmo@gmail.com
RD06/0020/0051
RD06/0020/0020
IDIBAPS-Centre Esther Koplowitz
Hospital Universitario Puerta de Hierro-Majadahonda
josep.roma@vhir.org
oromero@idibell.cat
RD06/0020/1021
RD06/0020/0062
Institut Recerca Vall Hebron (VHIR)
Programa Epigenetica i Biologia del Cancer-
PEBC, Bellvitge Biomedical Research Insititute-
IDIBELL
lromero-ibis@us.es
lrosich@clinic.cat
groue@clinic.ub.es
asagardo@unav.es
RD06/0020/0013
RD06/0020/0014
RD06/0020/0014
RD06/0020/0088
Instituto de Biomedicina de Sevilla (IBiS)
Hospital Clínic- IDIBAPS
Hospital Clínic- IDIBAPS
Centro de Investigacion Médica Aplicada
(CIMA)
cristina.saiz@ciemat.es
isalaver@clinic.ub.es
RD06/0020/0029
RD06/0020/0039
CIEMAT
Institut d’Investigacions August Pi i Sunyer –
IDIBAPS / Hospital Clinic
csanmillan@idiphim.org RD06/0020/0020 Hospital Universitario Puerta de Hierro-Majadahonda
mscespedes@idibell.cat RD06/0020/0062 Programa Epigenetica i Biologia del Cancer-
PEBC, Bellvitge Biomedical Research Insititute-
IDIBELL
tania.sanchez@cabimer.es RD06/0020/0068 Centro Andaluz de Biología Molecular y Medicina
Regenerativa- CABIMER
esantos@usal.es
RD06/0020/0000 Centro de Investigacion del Cáncer de Salamanca
(CIC-IBMCC; USAL-CSIC)
miguel.segura@vhir.org
tamara.sequeiros@vhir.org
RD06/0020/1021
RD06/0020/0058
Institut Recerca Vall Hebron (VHIR)
Institut de Recerca Hospital Universitari Vall
Hebron
marta.sese@vhir.org
carla.sole.canyadas@gmail.
com
RD06/0020/0104
RD06/0020/0014
Institut Recerca Vall Hebron (VHIR)
Hospital Clínic- IDIBAPS
fsole@carrerasresearch.org
aroa.soriano@vhir.org
estanzani@idibell.cat
xspuente@uniovi.es
RD07/0020/2004
RD06/0020/1021
RD06/0020/0097
INSTITUT DE RECERCA JOSEP CARRERAS
Institut Recerca Vall Hebron (VHIR)
IDIBELL-Universitat de Barcelona
Department of Biochemistry, University of
Oviedo
Eduardo.tormo@uv.es
atortosa@ub.edu
uso_mar@gva.es
RD06/0020/0080
RD06/0020/0097
RD06/0020/1024
Hospital Clinico Universitario de Valencia
IDIBELL-Universitat de Barcelona
Hospital General de Valencia
Maria Carmela MCVEGLIA@clinic.ub.es
Institut d’Investigacions August Pi i Sunyer –

Apellidos Nombre E-mail Grupo RTICC Centro
Vera Arroyo
Vicario
Vidal Crespo
Xargay Torrent
Serafín Eduardo seduvar@gmail.com
Rocio
rvicario@vhio.net
Anna
AVIDALC@clinic.ub.es
Sílvia
sxargay@clinic.cat
RD06/0020/0097
RD06/0020/0022
RD06/0020/0051
RD06/0020/0014
IDIBELL-Universitat de Barcelona
Instituto de Oncologia Vall d’Hebron (VHIO)
IDIBAPS-Centre Esther Koplowitz
Hospital Clínic- IDIBAPS
98