@article{550c7acb000f4f33935b974a0eff57db,
title = "Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma",
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.",
author = "Arthur, {Sarah E.} and Aixiang Jiang and Grande, {Bruno M.} and Miguel Alcaide and Razvan Cojocaru and Rushton, {Christopher K.} and Anja Mottok and Hilton, {Laura K.} and Lat, {Prince Kumar} and Zhao, {Eric Y.} and Luka Culibrk and Daisuke Ennishi and Selin Jessa and Lauren Chong and Nicole Thomas and Prasath Pararajalingam and Barbara Meissner and Merrill Boyle and Jordan Davidson and Bushell, {Kevin R.} and Daniel Lai and Pedro Farinha and Slack, {Graham W.} and Morin, {Gregg B.} and Sohrab Shah and Dipankar Sen and Jones, {Steven J.M.} and Mungall, {Andrew J.} and Gascoyne, {Randy D.} and Audas, {Timothy E.} and Peter Unrau and Marra, {Marco A.} and Connors, {Joseph M.} and Christian Steidl and Scott, {David W.} and Morin, {Ryan D.}",
note = "Funding Information: British Columbia Cancer Centre for Lymphoid Cancer gratefully acknowledges research funding support from the Terry Fox Research Institute (1043), Genome Canada, Genome British Columbia, the Canadian Institutes for Health Research, and the British Columbia Cancer Foundation. This work was supported by a Terry Fox New Investigator Award (1021) and an operating grant from the Canadian Institutes for Health Research (CIHR) to RDM, who is supported by a New Investigator award from CIHR and a Michael Smith Foundation for Health Research Scholar award. The genome sequence data and RNA-seq was produced with support from a contract with Genome Canada and Genome British Columbia led by JMC. MAM acknowledges the support of the Canada Research Chairs program and CIHR Foundation grant FDN-143288. The results published here are in whole or part based upon data generated by the TCGA Research Network: http:// cancergenome.nih.gov/. We gratefully acknowledge TCGA and all providers of samples and resources for generating this valuable resource. The TCGA exome data was obtained through Database of Genotypes and Phenotypes (phs000178.v9.p8 and phs000450.v2. p1). We also acknowledge the ICGC MALY-DE project for providing access to their unpublished data. Aligned reads for those genomes were obtained through a DACO-approved project (to RDM) using a virtual instance on the Cancer Genome Collabora-tory. Some of these data were produced as part of the Slim Initiative for Genomic Medicine (SIGMA), a joint US-Mexico project funded by the Carlos Slim Health Institute. AM is supported by fellowships from the Mildred-Scheel-Cancer-Foundation (German Cancer Aid), the MSFHR and Lymphoma Canada. The authors gratefully acknowledge the patient donors of samples used herein. We also thank Dr. Matthew Morin at Keyano College for the formal description of the rainstorm algorithm. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-06354-3",
language = "English",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
