In:
PLOS ONE, Public Library of Science (PLoS), Vol. 16, No. 5 ( 2021-5-4), p. e0248886-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0248886
DOI:
10.1371/journal.pone.0248886.g001
DOI:
10.1371/journal.pone.0248886.g002
DOI:
10.1371/journal.pone.0248886.g003
DOI:
10.1371/journal.pone.0248886.g004
DOI:
10.1371/journal.pone.0248886.s001
DOI:
10.1371/journal.pone.0248886.s002
DOI:
10.1371/journal.pone.0248886.s003
DOI:
10.1371/journal.pone.0248886.s004
DOI:
10.1371/journal.pone.0248886.s005
DOI:
10.1371/journal.pone.0248886.s006
DOI:
10.1371/journal.pone.0248886.s007
DOI:
10.1371/journal.pone.0248886.s008
DOI:
10.1371/journal.pone.0248886.s009
DOI:
10.1371/journal.pone.0248886.s010
DOI:
10.1371/journal.pone.0248886.s011
DOI:
10.1371/journal.pone.0248886.s012
DOI:
10.1371/journal.pone.0248886.s013
DOI:
10.1371/journal.pone.0248886.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2267670-3
Permalink