H3K36 methyltransferases can either support or suppress self-renewal, at least in some settings, through mechanisms that are also active in normal stem cells.112 SET domain containing 2, histone lysine methyltransferase (SETD2) is frequently mutated in multiple neoplasms, including breast and lung cancers, and contributes to cancer progression through increased stemness and dysregulation of differentiation pathways. The gene discussed is SETD2; the disease is neoplasm.