VHL and renal cell carcinoma: Based on the previous reports that loss of VHL protein didn’t promote tumor growth in primary cells but did lead to extremely proliferative xenografts of renal cell carcinoma (RCC) cell lines [7], we hypothesize that loss of Vhl gene in hemangioblast-derived cells is sufficient for the initiation of de novo tumorigenesis of VHL-associated hemangioblastoma, while additional mutations and/or environmental factors are needed for the tumor progression.