These findings integrate SETD2 into the p53 regulatory network and provide a reasonable explanation for the intriguing observation that inactivation of this master regulator of cell cycle checkpoints in ccRCC is rarely caused by mutations in TP53 (Gurova et al., 2004; Dalgliesh et al., 2010; Sato et al., 2013). Here, SETD2 is linked to nonpapillary renal cell carcinoma.