Genome-wide Detection of Genes Targeted by Aberrant Somatic Hypermutation in Lymphoma

We report a novel approach to identify genome-wide somatic hypermutation hotspots from short Illumina H3K4me3 ChIPseq reads in diffuse large B-cell lymphoma cells (DLBCL). Abberant somatic hypermation are known to occur at the promoters of several proto-oncogenes in DLBCL. To identify such events genome-wide, we performed H3K4me3 ChIPseq experiments (as to enrich promoter sequences of actively transcribed genes) in 2 DLBCL cells lines (OCI-Ly1 and OCI-Ly8) and their normal B-cell counterparts, Naive B cells (NBC) and Germinal Center B cells (GCBs). We discover new genes that harbor mutations in their promoter regions that are potentially introduced by the aberrant activation-induced cytosine deaminase activity in lymphoma cell lines, and many of these genes are important for the B cell biology. Moreover, we show that these mutations can affect the activities of these promoters. Our study provides a feasible approach for the detection of promoter mutations and broadens our knowledge on promoter mutations in lymphomas. Overall design: Examination of 1 histone mark (H3K4me3) in 4 different cell types.