discovered that the Von Hippel-Lindau (VHL) gene is mutated in more than 80% of renal cell carcinomas owing to promoter methylation, resulting in VHL protein dysfunction, which in turn induces hypoxia-inducible factor (HIF) activation and leads to abnormal expression of downstream vascular endothelial growth factor (VEGF) (8–10). This evidence concerns the gene VHL and hereditary clear cell renal cell carcinoma.