The loss of VHL also leads to the transcription of HIF-2α which is involved in overexpressing hypoxia-inducible genes including VEGF, the platelet-derived growth factor-β (PDGF-β), and transforming the growth factor-α (TGF-α) which are all involved in ccRCC tumorigenesis (Figure 1) [85,86]. This evidence concerns the gene SESN2 and nonpapillary renal cell carcinoma.