Characterization and Functional Significance of the von Hippel-Lindau Gene in Renal Cell Carcinomas
The von Hippel-Lindau (VHL) syndrome is an autosomal dominant inherited pleiotropic disorder with virtually complete penetrance and highly variable expressivity. Carriers of the gene have increased susceptibility to a variety of neoplasms of mesodermal and neuroectodermal origin. The most characteristic and frequently observed lesions in VHL are angiomatosis retinae (52%–58%), cerebellar and spinal hemangioblastoma (38%–66%), pheochromocytoma (17%–26%), pancreatic and renal cysts (8%–72% and 25%–60%, respectively;  and others). Of those affected by the syndrome, 17%–55% suffer from renal cell carcinoma (RCC), which is one of the most serious and life-threatening complications of the disease. Compared to counterparts with the sporadic form, RCCs in VHL patients occur at an earlier age and are often bilateral or multifocal and are associated with renal cysts. In contrast to simple cysts in the general population, which are usually benign, renal cysts in VHL may contain occult carcinomas. After onset the malignant potential of RCC in VHL is similar to that in the sporadic type, often complicated by metastasis and de novo recurrences. While many VHL patients survive surgery of hemangioblastoma, up to one-third of these patients die of RCC. The incidence of VHL is approximately 1:100000, but it is possible that there are geographic variations, with a regional incidence of 1:40 000. There is as yet no sufficient explanation for the primary biochemical defect in VHL or for the variable constellation of tissue type involved in tumor formation. Recent advances in tumor cytogenetics and molecular genetics provide the tools necessary to search for genetic defects in VHL. With the advent of reverse genetics it has become possible to isolate and characterize genes of interest without any hint of their possible functions.
KeywordsRecombination Adenoma Electrophoresis Retina Retinoblastoma
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