Genetic features associated with RelB activation in DLBCL. (A) The mutational heatmap indicates 26 recurrently altered genes in ABC and GCB DLBCL cases (GSE87371, n = 156) with frequency >5%. To the right of the mutational heatmap is shown the prevalence of the indicated mutated genes in RelB-positive vs RelB-negative DLBCL cases as defined by using GEP. P value by Fisher’s exact test, significance thresholds, P < .05, false discovery rate [FDR] (q value) < 0.1. Color codes indicate the presence or absence of the corresponding feature. RelB activation status and ABC vs GCB DLBCL subtypes are indicated above the mutational map. (B) Volcano plot depicting the differences of gene mutations between RelB-positive and RelB-negative DLBCLs as defined by GEP (x-axis, log₂ odds ratio; y-axis, –log₁₀P value >1). P value by Fisher’s exact test; significance thresholds, P < .05, FDR (q value) < 0.1. (C) Correlation of Bcl6, Bcl2, or Myc fusion as evaluated by fluorescence in situ hybridization with RelB gene expression signature, n = 107 patients. P value by Fisher’s exact test; significance thresholds, P < .05, FDR (q value) < 0.1. Color codes indicate the presence or absence of the corresponding feature. (D) Top: prevalence of the indicated genetic subtypes defined according to the LymphGen algorithm (https://explore.openaire.eu) within the RelB-positive and RelB-negative clusters as defined by using GEP (n = 168). Bottom: prevalence of RelB-binding activity as evaluated by using GEP within the indicated LymphGen genetic subtypes (n = 168). (E) Top: prevalence of the indicated genetic subtypes defined by the LymphGen algorithm within each canonical NF-κB DNA-binding subgroup (RelA and cRel). Bottom: prevalence of canonical NF-κB DNA-binding subgroups (RelA and cRel) within the indicated LymphGen genetic subtype. (F) Mutational heatmap for TRAF3, TRAF2, MAP3K14, NFKBIA, and NFKBIZ, 5 important regulators of NF-κB activation. To the right of the mutational heatmap is shown the prevalence of the indicated mutated genes in RelB-positive vs RelB-negative DLBCL cases as defined by EMSA (n = 64). P value by Fisher’s exact test; significance thresholds, P < .05, FDR (q value) < 0.1. Color codes indicate the presence or absence of the corresponding feature. RelB activation status is indicated above the mutational map.