The synergistic effect of heterozygous Crebbp/Kmt2d loss in perturbing the GC response (a phenotype not observed when these genes are individually monoallelically deleted at this stage) and the identification of shared and specific CREBBP/KMT2D-bound chromatin domains offer a mechanistic explanation to the frequent concurrent selection of these alterations in lymphoma. The gene discussed is CREBBP; the disease is lymphoma.