Alternatively, leveraging refined cell-of-origin (COO) subtyping including the dark-zone signature positive (DZsig+) classification [17] to facilitate comparative analysis of genomic and transcriptomic alterations within tumor sub-groups, we identify GCB and DZsig+ subtype rrDLBCL tumors more frequently observed in aggressive, primary treatment refractory, cases with differential underlying biology defined by enrichment for somatic variants and copy number alterations affecting MYC, BCL2, BCL6 and TP53 among additional strong lymphoma driver genes. The gene discussed is BCL2; the disease is lymphoma.