CDKN2A/B, which encodes CDK4/6 inhibitors p16 and p15, is inactivated by mutations or hypermethylation in a subset of ccRCC, and CDKN2A/B loss cooperates with VHL loss to promote ccRCC in mice (4, 26, 54, 55). Here, CDK4 is linked to nonpapillary renal cell carcinoma.