New Insights into von Hippel-Lindau Function Highlighted by Investigation of the Trichloroethylene-Induced p.P81S Hotspot Mutation
Menée in vivo, cette étude met en évidence divers mécanismes par lesquels la mutation P81S du gène VHL favorise la croissance d'un carcinome rénal à cellules claires associé à une exposition professionelle au trichloroéthylène
The von Hippel-Lindau gene (VHL), composed of three exons, encodes a protein, pVHL, with diverse tumor suppressor activities. Germline VHL mutations are found in patients with von Hippel-Lindau (VHL), an autosomal dominant hereditary cancer syndrome in which affected individuals are at risk for the development of highly vascularized benign and malignant tumors including central nervous system hemangioblastomas, retinal hemangiomas, clear cell renal carcinomas (ccRCCs), pheochromocytomas, and pancreatic neuroendocrine tumors (1). Biallelic inactivation of VHL, whether via mutation or promoter methylation, is found in VHL-associated tumors and in nearly 90% of sporadic ccRCC tumors (2,3), the most common form of sporadic kidney cancer...