Heterozygous missense mutations resulting in the substitution of tyrosine 641 (Y641) within the SET domain of EZH2 were noted in 22% of patients with diffuse large B-cell lymphoma (DLBCL), and this mutation conferred increased histone methylation catalytic activity, while loss-of-function mutations in EZH2 conferred a poor prognosis in myeloid malignancies and T-cell acute lymphoblastic leukemia82–84. Here, SET is linked to diffuse large B-cell lymphoma.