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Genome-Wide Discovery of Somatic Regulatory Variants in Diffuse Large B-Cell Lymphoma

Resource type
Date created
2018-10-01
Authors/Contributors
Author (aut): Arthur, Sarah E.
Author (aut): Jiang, Aixiang
Author (aut): Grande, Bruno M.
Author (aut): Alcaide, Miguel
Author (aut): Cojocaru, Razvan
Author (aut): Mottok, Anja
Author (aut): Hilton, Laura K.
Author (aut): Lat, Prince Kumar
Author (aut): Zhao, Eric Y.
Author (aut): Culibrk, Luka
Author (aut): Ennishi, Daisuke
Author (aut): Jessa, Selin
Author (aut): Chong, Lauren
Author (aut): Thomas, Nicole
Author (aut): Meissner, Barbara
Author (aut): Boyle, Merrill
Author (aut): Davidson, Jordan
Author (aut): Bushell, Kevin R.
Author (aut): Lai, Daniel
Author (aut): Farinha, Pedro
Author (aut): Slack, Graham W.
Author (aut): Morin, Gregg B.
Author (aut): Shah, Sohrab
Author (aut): Sen, Dipankar
Author (aut): Jones, Steven
Author (aut): Mungall, Andrew J.
Author (aut): Gascoyne, Randy D.
Author (aut): Audas, Timothy E.
Author (aut): Unrau, Peter
Author (aut): Marra, Marco A.
Author (aut): Connors, Joseph M.
Author (aut): Steidl, Christian
Author (aut): Scott, David W.
Author (aut): Morin, Ryan D.
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.
Document
Published as
Arthur, S. E., Jiang, A., Grande, B. M., Alcaide, M., Cojocaru, R., Rushton, C. K., … Morin, R. D. (2018). Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma. Nature Communications, 9(1), 4001. doi: 10.1038/s41467-018-06354-3
Publication title
Nature Communications
Document title
Genome-Wide Discovery of Somatic Regulatory Variants in Diffuse Large B-Cell Lymphoma
Date
2018
Volume
9
Issue
1
Publisher DOI
10.1038/s41467-018-06354-3
Copyright statement
Copyright is held by the author(s).
Scholarly level
Peer reviewed?
Yes
Language
English
Member of collection
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