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

Joan Enric Ramis-Zaldivar, Blanca Gonzalez-Farré, Olga Balagué, Verónica Celis, Ferran Nadeu, Julia Salmerón-Villalobos, Mara Andrés, Idoia Martin-Guerrero, Marta Garrido-Pontnou, Ayman Gaafar, Mariona Suñol, Carmen Bárcena, Federico Garcia-Bragado, Maitane Andión, Daniel Azorín, Itziar Astigarraga, Maria Sagaseta de Ilurdoz, Constantino Sábado, Soledad Gallego, Jaime Verdú-AmorósRafael Fernandez-Delgado, Vanesa Perez, Gustavo Tapia, Anna Mozos, Montserrat Torrent, Palma Solano-Páez, Alfredo Rivas-Delgado, Ivan Dlouhy, Guillem Clot, Anna Enjuanes, Armando López-Guillermo, Pallavi Galera, Matthew J. Oberley, Alanna Maguire, Colleen Ramsower, Lisa M. Rimsza, Leticia Quintanilla-Martinez, Elaine S. Jaffe, Elías Campo, Itziar Salaverria

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)274-286
Number of pages13
JournalBlood
Volume135
Issue number4
DOIs
StatePublished - Jan 23 2020

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Distinct molecular profile of IRF4-rearranged large B-cell lymphoma'. Together they form a unique fingerprint.

Cite this