TY - JOUR
T1 - Distinct molecular profile of IRF4-rearranged large B-cell lymphoma
AU - Ramis-Zaldivar, Joan Enric
AU - Gonzalez-Farré, Blanca
AU - Balagué, Olga
AU - Celis, Verónica
AU - Nadeu, Ferran
AU - Salmerón-Villalobos, Julia
AU - Andrés, Mara
AU - Martin-Guerrero, Idoia
AU - Garrido-Pontnou, Marta
AU - Gaafar, Ayman
AU - Suñol, Mariona
AU - Bárcena, Carmen
AU - Garcia-Bragado, Federico
AU - Andión, Maitane
AU - Azorín, Daniel
AU - Astigarraga, Itziar
AU - de Ilurdoz, Maria Sagaseta
AU - Sábado, Constantino
AU - Gallego, Soledad
AU - Verdú-Amorós, Jaime
AU - Fernandez-Delgado, Rafael
AU - Perez, Vanesa
AU - Tapia, Gustavo
AU - Mozos, Anna
AU - Torrent, Montserrat
AU - Solano-Páez, Palma
AU - Rivas-Delgado, Alfredo
AU - Dlouhy, Ivan
AU - Clot, Guillem
AU - Enjuanes, Anna
AU - López-Guillermo, Armando
AU - Galera, Pallavi
AU - Oberley, Matthew J.
AU - Maguire, Alanna
AU - Ramsower, Colleen
AU - Rimsza, Lisa M.
AU - Quintanilla-Martinez, Leticia
AU - Jaffe, Elaine S.
AU - Campo, Elías
AU - Salaverria, Itziar
N1 - Publisher Copyright:
© 2020 American Society of Hematology. All rights reserved.
PY - 2020/1/23
Y1 - 2020/1/23
N2 - 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-kB 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.
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-kB 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.
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U2 - 10.1182/blood.2019002699
DO - 10.1182/blood.2019002699
M3 - Article
C2 - 31738823
AN - SCOPUS:85078373918
SN - 0006-4971
VL - 135
SP - 274
EP - 286
JO - Blood
JF - Blood
IS - 4
ER -