Indexed in

License and use

Citations

Cited 98 times in

Cited 94 times in

Cited 40 times in

Cited 92 times in

Altmetrics

Grant support

This work was supported by Asociacion Espanola Contra el Cancer (AECC CICPFI6025SALA), Fondo de Investigaciones Sanitarias Instituto de Salud Carlos III (Miguel Servet Program CP13/00159 and PI15/00580 to I.S.), Spanish Ministerio de Economia y Competitividad (SAF201564885-R to E.C.), Generalitat de Catalunya Suport Grups de Recerca (2017-SGR-1107 to I.S. and 2017-SGR-1142 to E.C.), SPECS II grant (National Cancer Institute 1U01CA157581), and the European Regional Development Fund (Una manera de fer Europa). J.E.R.-Z. was supported by a fellowship from Generalitat de Catalunya AGAUR FI-DGR 2017 (2017 FI_B01004). E.C. is an Academia Researcher of the Institucio ' Catalana de Recerca i Estudis Avancats of the Generalitat de Catalunya. This work was developed at the Centro Esther Koplowitz, Barcelona, Spain. The group is supported by Accioinstrumental d'incorporacio de cientifics i tecnolegs PERIS 2016 (SLT002/16/00336 to Noelia Garcia) from Generalitat de Catalunya.

Analysis of institutional authors

Share

Distinct molecular profile of IRF4-rearranged large B-cell lymphoma

Publicated to:Blood. 135 (4): 274-286 - 2020-01-23 135(4), DOI: 10.1182/blood.2019002699

Authors: Enric Ramis-Zaldivar, Joan; Gonzalez-Farre, Blanca; Balague, Olga; Celis, Veronica; Nadeu, Ferran; Salmeron-Villalobos, Julia; Andres, Mara; Martin-Guerrero, Idoia; Garrido-Pontnou, Marta; Gaafar, Ayman; Sunol, Mariona; Barcena, Carmen; Garcia-Bragado, Federico; Andion, Maitane; Azorin, Daniel; Astigarraga, Itziar; Sagaseta de Ilurdoz, Maria; Sabado, Constantino; Gallego, Soledad; Verdu-Amoros, Jaime; Fernandez-Delgado, Rafael; Perez, Vanesa; Tapia, Gustavo; Mozos, Anna; Torrent, Montserrat; Solano-Paez, Palma; Rivas-Delgado, Alfredo; Dlouhy, Ivan; Clot, Guillem; Enjuanes, Anna; Lopez-Guillermo, Armando; Galera, Pallavi; Oberley, Matthew J; Maguire, Alanna; Ramsower, Colleen; Rimsza, Lisa M; Quintanilla-Martinez, Leticia; Jaffe, Elaine S; Campo, Elias; Salaverria, Itziar

Affiliations

Abstract

Pediatric large B-cell lymphomas (LBCL) 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 large B-cell lymphomas, not otherwise specified (DLBCL, NOS), 20 LBCL-IRF4, and 12 high grade B-cell lymphomas, NOS (HGBCL, NOS) in patients {less than or equal to}25 years-old 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 chr7, 11q12.3-q25 whereas DLBCL,NOS were predominantly of germinal center B-cell (GCB) subtype and carried gene mutations similar to the adult counterpart (e.g. 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 >18y old, activated B-cell 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/young-adult LBCL, improve the classification of this group of tumors and provide new parameters for risk stratification.Copyright © 2019 American Society of Hematology.

Keywords