[Von Hippel-Lindau disease: recent advances in genetics and clinical management].

Von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome that predisposes to the development of a panel of highly vascularized tumors including CNS and retinal hemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), pheochromocytomas and pancreatic neuroendocrine tumors. CNS hemangioblastomas and RCC are the two main life-threatening manifestations. The disease is caused by germline mutations in the VHL tumor-suppressor gene that plays a major role in regulating the oxygen-sensing pathway by targeting the hypoxia-inducible factor HIF for degradation in proteasome. Somatic inactivation of the VHL gene occurs also in most sporadic RCC and sporadic CNS hemangioblastomas. The demonstration of the critical role of VHL in angiogenesis is paving the way for the development of new specific drugs that could represent an attractive potential treatment for VHL but also for sporadic RCC and other cancers.