What gene is disrupted in the majority of sporadic cases of RCC?
The VHL gene is disrupted in up to 70% of sporadic cases of RCC. In approximately 50% of cases, somatic mutations occur, and in 10% to 20% of cases, the gene is hypermethylated.
A consequence of VHL mutation is upregulation of hypoxia-induced genes, leading to increased production of moieties such as vascular endothelial growth factor (VEGF). This, in turn, causes increased tumor angiogenesis.