Untitled - Red Temática de investigación cooperativa en cáncer

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’ (