Genome-wide discovery of somatic coding and regulatory variants in Diffuse Large B-cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Many known driver mutations are over-represented in one of its two molecular subgroups, knowledge of which has aided in the development of therapeutics that target these features. The heterogeneity of DLBCL determined through prior genomic analysis suggests an incomplete understanding of its molecular aetiology, with a limited diversity of genetic events having thus far been attributed to the activated B-cell (ABC) subgroup. Through an integrative genomic analysis we uncovered genes and non-coding loci that are commonly mutated in DLBCL including putative regulatory sequences. We implicate recurrent mutations in the 3′UTR of NFKBIZ as a novel mechanism of oncogene deregulation and found small amplifications associated with over-expression of FC-γ receptor genes. These results inform on mechanisms of NF-κB pathway activation in ABC DLBCL and may reveal a high-risk population of patients that might not benefit from standard therapeutics.