Changes in 5mC were conserved in primary ccRCC with biallelic SETD2 inactivation, in SETD2-mutant papillary RCC (a distinct tumor of the kidney), and in lung adenocarcinomas with SETD2 mutations, and resulted in a distinct 5mC signature that efficiently clustered tumors by SETD2 genotype and higher tumor grade and stage, consistent with findings by us [2, 13] and others [37-39] that SETD2 mutations are generally linked to poor prognosis and/or metastasis. The gene discussed is SETD2; the disease is neoplasm.