Format

Send to

Choose Destination
Nat Commun. 2018 Oct 1;9(1):4001. doi: 10.1038/s41467-018-06354-3.

Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma.

Author information

1
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada.
2
Lymphoid Cancer Research, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
3
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada.
4
Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
5
Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
6
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, V5A 1S6, Canada. rdmorin@sfu.ca.
7
Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC, V5Z 1L3, Canada. rdmorin@sfu.ca.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3' UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NF-κB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor protein IIB), primarily in the germinal centre B-cell (GCB) subgroup, correlate with poor patient outcomes suggestive of a novel oncogene. These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.

PMID:
30275490
PMCID:
PMC6167379
DOI:
10.1038/s41467-018-06354-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center