Consistent with this observation, KDM5C mutations in ccRCC metastasis frequently arise together with different combinations of other recurrently altered ccRCC tumour suppressor genes including VHL, PBRM1, SETD2, TP53, PTEN or with the MTOR oncogene (Supplementary Fig. 1c). Here, SETD2 is linked to nonpapillary renal cell carcinoma.