Untitled - Red Temática de investigación cooperativa en cáncer

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).