| Literature DB >> 30275490 |
Sarah E Arthur1,2, Aixiang Jiang1,2,3, Bruno M Grande1, Miguel Alcaide1, Razvan Cojocaru1, Christopher K Rushton1, Anja Mottok2, Laura K Hilton1, Prince Kumar Lat1, Eric Y Zhao2, Luka Culibrk2, Daisuke Ennishi2, Selin Jessa1, Lauren Chong2, Nicole Thomas1, Prasath Pararajalingam1, Barbara Meissner2, Merrill Boyle2, Jordan Davidson1, Kevin R Bushell1, Daniel Lai4, Pedro Farinha2, Graham W Slack2, Gregg B Morin3,5, Sohrab Shah4, Dipankar Sen1, Steven J M Jones1,3,4, Andrew J Mungall3, Randy D Gascoyne2, Timothy E Audas1, Peter Unrau1, Marco A Marra3,4, Joseph M Connors2, Christian Steidl2, David W Scott2, Ryan D Morin6,7.
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.Entities:
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Year: 2018 PMID： 30275490 PMCID： PMC6167379 DOI： 10.1038/s41467-018-06354-3
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919