Consistent with a tumor-suppressive function (12, 24, 26), PBRM1-deficient ccRCC tumors upregulate hypoxia-inducible factor (30, 31) and angiogenesis pathway transcription (32, 33, 34) to enhance tumor vascularity (35, 36). Here, PBRM1 is linked to nonpapillary renal cell carcinoma.