Recurrently altered genes identified in diagnostic and rrDLBCL. Collection of 2 DLBCL cohorts representing various chemo-immunotherapy treatment profiles allowed for the division into 3 biopsy types prior to genomic alteration analyses by WES (discovery cohort) or by targeted sequencing (validation cohort): Diagnostic DLBCL, representing initial diagnostic biopsies of patients that go on to have a durable response to RCHOP-like therapies; Diagnostic rrDLBCL, representing initial diagnostic biopsies of patients that progress or relapse after RCHOP-like therapies; and Relapsed rrDLBCL, representing relapse biopsies of patients who experienced refractory or relapsed disease. (A) Schematic overview of the sampling procedures for the 3 defined biopsy types of DLBCL. (B) Genes of interest identified by multiple mutation analyses including the MutSig2CV and IntOgen programs (n [cases] = 37; b [biopsies] = 45). Genes of interest have been organized into signaling/pathway categories (gray brackets). Mutations are shown as colored boxes. In cases where a gene had multiple mutations in the same patient, the mutation resulting in the most severe change to the protein structure is shown. Biopsies are listed horizontally and divided by biopsy type with multiple biopsies from the same patient placed adjacently. The number of mutations for each gene in the validation cohort is displayed as a histogram on the far right (n = 41; b = 46). Genes of interest identified through recurrent copy number alteration analysis (GISTIC2.0) (n = 42 in initial analysis, n = 37 displayed). Multiple genes involved in antigen processing and presentation were identified in the 6p21 cytoband. Each box represents a gene's total copy number state. Survival, subtype (including activated B-cell [ABC] like, germinal center B-cell [GCB] like, and primary mediastinal B-cell lymphoma [PMBCL]), translocation status, age, International Prognostic Index (IPI), and number of extranodal sites for each biopsy are displayed in the bottom rows.