We first analyzed two patient-derived xenografts (PDXs) and cell lines of GCB-DLBCL tumors, which either carry the Y646N mutant EZH2 allele in combination with KMT2D biallelic loss-of-function mutations (the PDXMUT and the cell line OCI-Ly1) or carry two WT alleles for both genes (PDXWT and the cell line OCI-Ly7). The gene discussed is EZH2; the disease is diffuse large B-cell lymphoma.