Indeed, the formation of both renal cysts and tumors was prevented upon inactivation of HIF-1α and HIF-2α in VHL-deficient mice, indicating their shared involvement during the initial stages of ccRCC development [55] whereas only the HIF-1α isoform was evident in normal tubular cells [56,57]. This evidence concerns the gene EPAS1 and nonpapillary renal cell carcinoma.