Models of Von Hippel-Lindau tumor suppressor disease specific activity

9553 Background: The Von Hippel-Lindau (VHL) syndrome is an autosomal dominant disorder characterized by mutations in a classical tumor suppressor gene (VHL). Clear cell renal cell carcinoma and hemangioblastoma without pheochromocytoma characterize VHL type 1 disease. VHL type 2 disease is characterized by the presence of pheochromocytoma and is further subdivided into type 2A (pheochromocytoma and hemangioblastoma), 2B (pheochromocytoma, renal cell carcinoma, and hemangioblastoma), and 2C (pheochromocytoma only). VHL has been implicated in cellular processes important for tumorigenesis, including cell cycle control, extra-cellular matrix remodeling, response to oxygen deprivation, and angiogenesis. The importance of VHL in each of these processes as they pertain to tumorigenesis is unknown. Methods: To address the hypothesis that pVHL performs multiple functions within the cell, and perturbation of individual functions via missense mutations contributes to the tissue specificity of the VHL syndrome tumo...