Mutational Analysis of Endothelial Cells Derived From von Hippel–Lindau-Related Renal Cancer

Extract

von Hippel–Lindau (VHL) disease is an autosomal dominant, inherited cancer syndrome that is characterized by extensively vascularized tumors, such as hemangioblastomas of the retina and central nervous system, renal cell carcinomas (RCCs), and pheochromocytomas (1). The VHL tumor suppressor gene was cloned in 1993 and is located at chromosome 3p25–3p26 (2). According to the two-hit hypothesis for tumor suppressor genes, inactivation of both alleles of the VHL gene leads to tumor formation. One copy of the VHL gene is mutated by inheritance, and the second hit causes inactivation of the remaining wild-type VHL gene (3).

Although the VHL protein is widely expressed in different organs and cell types, its expression could not be demonstrated in endothelial cells of normal tissue (4). Strong expression of the VHL protein, however, was observed in proliferating endothelial cells from placenta, lung metastases of pancreatic adenocarcinoma, the base of an esophageal ulcer, and sprouting microvessels of atherosclerotic lesions [(5); Los M: unpublished observations]. In human umbilical vein endothelial cells and in dermal microvascular endothelial cells, expression of VHL messenger RNA was detected by northern blot analysis (Los M: unpublished observations).