The Kidney Cancer (Von Hippel-Lindau) Tumor Suppressor Gene

Cancer results from the accumulation of alterations in the expression of a small number of critical genes. Like cancers of the breast, colon and prostate, kidney cancer occurs in both a hereditary and a sporadic (non-hereditary) form. The most commonly studied form of hereditary kidney cancer is that which occurs in the familial cancer syndrome, Von Hippel-Lindau (VHL) disease. Recently, defects in one particular gene have been shown to be responsible in families with VHL disease. This inherited cancer syndrome is characterized by the development of multiple tumors, including kidney cancer, kidney cysts, brain cancers and non-malignant tumors in the adrenal glands. Abnormalities of the VHL gene have also been identified in tumor tissue from the majority of examined cases of sporadic kidney cancer, a disease diagnosed in 25,000 to 30,000 Americans each year. NIH intramural investigators have recently made several key discoveries about the function of the VHL gene protein product. Recent experiments have shown that the VHL protein may be able to sense whether cells are communicating with each other and may control the changes in cells responsible for the ability of cancer cells to spread and to metastasize. These findings open new approaches to studies of cell growth regulation in normal and malignant cells and could lead to new ways to diagnose, prevent, and treat cancer.

In many VHL families, the diagnosis of VHL can now be made at birth by detection of VHL gene mutations in blood cells. The finding of frequent VHL gene mutations in tumor tissue from patients with sporadic kidney cancer provides the opportunity for scientists to significantly improve methods for diagnosis of kidney cancer by detecting such mutations, either in tissue removed at surgery or by biopsy or, potentially, by searching for VHL gene mutations in the urine or circulating cells of patients with this disease.

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