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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-?B pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fc? 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.

SUBMITTER: Arthur SE 

PROVIDER: S-EPMC6167379 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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

Arthur Sarah E SE   Jiang Aixiang A   Grande Bruno M BM   Alcaide Miguel M   Cojocaru Razvan R   Rushton Christopher K CK   Mottok Anja A   Hilton Laura K LK   Lat Prince Kumar PK   Zhao Eric Y EY   Culibrk Luka L   Ennishi Daisuke D   Jessa Selin S   Chong Lauren L   Thomas Nicole N   Pararajalingam Prasath P   Meissner Barbara B   Boyle Merrill M   Davidson Jordan J   Bushell Kevin R KR   Lai Daniel D   Farinha Pedro P   Slack Graham W GW   Morin Gregg B GB   Shah Sohrab S   Sen Dipankar D   Jones Steven J M SJM   Mungall Andrew J AJ   Gascoyne Randy D RD   Audas Timothy E TE   Unrau Peter P   Marra Marco A MA   Connors Joseph M JM   Steidl Christian C   Scott David W DW   Morin Ryan D RD  

Nature communications 20181001 1


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 th  ...[more]

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