Open AccessDetection of new drivers of frequent B-cell lymphoid neoplasms using an integrated analysis of whole genomes
Author(s) -
Adrián Mosquera Orgueira,
Roi Ferreiro Ferro,
José Ángel Díaz Arias,
Cristina Santos,
Beatriz Antelo Rodríguez,
Laura Bao Pérez,
Natalia Alonso Vence,
Ággeles Bendaña López,
Ayelén Melisa Blanco,
Paula Melero Valentín,
And Res Peleteiro Raindo,
Marcos Pérez López,
Manuel Mateo Pérez Encinas,
Marta Sonia González Pérez,
Marianela Rodríguez,
José L. López
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0248886
Subject(s) - biology , lymphoma , b cell , follicular lymphoma , gene , lymphoproliferative disorders , genetics , diffuse large b cell lymphoma , cancer research , somatic hypermutation , genome , computational biology , immunology , antibody
B-cell lymphoproliferative disorders exhibit a diverse spectrum of diagnostic entities with heterogeneous behaviour. Multiple efforts have focused on the determination of the genomic drivers of B-cell lymphoma subtypes. In the meantime, the aggregation of diverse tumors in pan-cancer genomic studies has become a useful tool to detect new driver genes, while enabling the comparison of mutational patterns across tumors. Here we present an integrated analysis of 354 B-cell lymphoid disorders. 112 recurrently mutated genes were discovered, of which KMT2D , CREBBP , IGLL5 and BCL2 were the most frequent, and 31 genes were putative new drivers. Mutations in CREBBP , TNFRSF14 and KMT2D predominated in follicular lymphoma, whereas those in BTG2 , HTA-A and PIM1 were more frequent in diffuse large B-cell lymphoma. Additionally, we discovered 31 significantly mutated protein networks, reinforcing the role of genes such as CREBBP , EEF1A1 , STAT6 , GNA13 and TP53 , but also pointing towards a myriad of infrequent players in lymphomagenesis. Finally, we report aberrant expression of oncogenes and tumor suppressors associated with novel noncoding mutations ( DTX1 and S1PR2 ), and new recurrent copy number aberrations affecting immune check-point regulators ( CD83 , PVR ) and B-cell specific genes ( TNFRSF13C ). Our analysis expands the number of mutational drivers of B-cell lymphoid neoplasms, and identifies several differential somatic events between disease subtypes.