Mutational spectra of dark-zone DLBCL. (A-C) Venn diagrams showing the overlap in cases classified as MHG and DZsig across DLC (A), HMDS (B), and REMoDL-B (C) cohorts. Percentages are relative to the total number of cases classified as GCB-DLBCL in each cohort, and the size of each circle is proportional to the number of cases. Numbers outside the circles indicate GCB-DLBCL not classified as MHG or DZsig. (D) The mutational profile of GCB COO tumors across genes mutated in at least 10% of GCB tumors, stratified according to GEP classifications and annotated according to the published LymphGen or HMRN genetic classification and cohort. (E) Enrichment for coding or hotspot mutations among the genes shown in panel D. Positive values in the forest plot (left panel) indicate enrichment relative to GCB-DLBCL. The percentage of tumors within each group harboring 1 or more coding mutation per gene is shown in the right panel. MHG includes all MHG-classified tumors (MHG and DZsig&MHG) and DZsig includes all DZsig tumors (DZsig and DZsig&MHG). CREBBP∗: missense mutations in the CREBBP KAT domain. EZH2∗: Mutations at Y646 in EZH2. (F) The proportion of tumors belonging to each GEP classification group classified as EZB by the LymphGen classifier across the DLC and HMDS cohorts, separating MHG-only, DZsig-only, and DZsig&MHG tumors. ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001. (G) The percentage of tumors belonging to each GEP classification group is classified as BCL2 by the HMRN classifier, separating MHG, DZsig, and DZsig&MHG tumors. No comparisons reached statistical significance.