Taken together, these observations support a genotype-phenotype link in RCC, since the hypervascularity of these tumors can be explained by a pVHL-dependent defect in ubiquitin-mediated degradation of HIFα proteins, leading to increased HIF-1 transcriptional activity with consequent upregulation of VEGF and other factors that are thought to promote survival (reviewed in 57) [57,64-66] (Figure 2). This evidence concerns the gene HIF1A and renal cell carcinoma.