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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. 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 NFκB 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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003783 Illumina HiSeq 2000 Illumina HiSeq 2500 376
EGAD00001004142 146
Publications Citations
Genome-wide discovery of somatic regulatory variants in diffuse large B-cell lymphoma.
Nat Commun 9: 2018 4001
74
The Identification and Interpretation of cis-Regulatory Noncoding Mutations in Cancer.
High Throughput 8: 2018 E1
3
IgCaller for reconstructing immunoglobulin gene rearrangements and oncogenic translocations from whole-genome sequencing in lymphoid neoplasms.
Nat Commun 11: 2020 3390
21
Super-enhancer hypermutation alters oncogene expression in B cell lymphoma.
Nature 607: 2022 808-815
22