RT Journal Article
T1 Distinct molecular profile of IRF4-rearranged large B-cell lymphoma.
A1 Ramis-Zaldivar, Joan Enric
A1 Gonzalez-Farré, Blanca
A1 Balagué, Olga
A1 Celis, Verónica
A1 Nadeu, Ferran
A1 Salmerón-Villalobos, Julia
A1 Andrés, Mara
A1 Martin-Guerrero, Idoia
A1 Garrido-Pontnou, Marta
A1 Gaafar, Ayman
A1 Suñol, Mariona
A1 Bárcena, Carmen
A1 Garcia-Bragado, Federico
A1 Andión, Maitane
A1 Azorín, Daniel
A1 Astigarraga, Itziar
A1 Sagaseta de Ilurdoz, Maria
A1 Sábado, Constantino
A1 Gallego, Soledad
A1 Verdú-Amorós, Jaime
A1 Fernandez-Delgado, Rafael
A1 Perez, Vanesa
A1 Tapia, Gustavo
A1 Mozos, Anna
A1 Torrent, Montserrat
A1 Solano-Páez, Palma
A1 Rivas-Delgado, Alfredo
A1 Dlouhy, Ivan
A1 Clot, Guillem
A1 Enjuanes, Anna
A1 López-Guillermo, Armando
A1 Galera, Pallavi
A1 Oberley, Matthew J
A1 Maguire, Alanna
A1 Ramsower, Colleen
A1 Rimsza, Lisa M
A1 Quintanilla-Martinez, Leticia
A1 Jaffe, Elaine S
A1 Campo, Elías
A1 Salaverria, Itziar
AB Pediatric large B-cell lymphomas (LBCLs) share morphological and phenotypic features with adult types but have better prognosis. The higher frequency of some subtypes such as LBCL with IRF4 rearrangement (LBCL-IRF4) in children suggests that some age-related biological differences may exist. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse LBCLs (DLBCLs), not otherwise specified (NOS); 20 LBCL-IRF4 cases; and 12 cases of high-grade B-cell lymphoma (HGBCL), NOS in patients ≤25 years using an integrated approach, including targeted gene sequencing, copy-number arrays, and gene expression profiling. Each subgroup displayed different molecular profiles. LBCL-IRF4 had frequent mutations in IRF4 and NF-κB pathway genes (CARD11, CD79B, and MYD88), losses of 17p13 and gains of chromosome 7, 11q12.3-q25, whereas DLBCL, NOS was predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (eg, SOCS1 and KMT2D), gains of 2p16/REL, and losses of 19p13/CD70. A subset of HGBCL, NOS displayed recurrent alterations of Burkitt lymphoma-related genes such as MYC, ID3, and DDX3X and homozygous deletions of 9p21/CDKN2A, whereas other cases were genetically closer to GCB DLBCL. Factors related to unfavorable outcome were age >18 years; activated B-cell (ABC) DLBCL profile, HGBCL, NOS, high genetic complexity, 1q21-q44 gains, 2p16/REL gains/amplifications, 19p13/CD70 homozygous deletions, and TP53 and MYC mutations. In conclusion, these findings further unravel the molecular heterogeneity of pediatric and young adult LBCL, improve the classification of this group of tumors, and provide new parameters for risk stratification.
YR 2020
FD 2020
LK http://hdl.handle.net/10668/14704
UL http://hdl.handle.net/10668/14704
LA en
DS RISalud
RD Apr 18, 2025