von Hippel-Lindau Gene Mutations in Human and Rodent Renal Tumors—Association With Clear Cell Phenotype

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Renal cell carcinoma (RCC) is the most common cancer in the adult kidney, accounting for about 85% of all renal cancers. It is estimated that in 1998, there will be approximately 29 900 new cases of RCC diagnosed in the United States (17 600 in men and 12 300 in women), and 11 000 people will die of RCC ( 1 ) . Risk factors for developing RCC include cigarette smoking and hypertension ( 2 ) as well as obesity, diet, end-stage renal disease, and occupational exposure to asbestos or cadmium ( 3 , 4 ) . With an incidence rate that has increased more than 45% between 1973 and 1995 ( 5 ) , gaining an understanding of the etiology of this disease is clearly important.

There are several genetic diseases associated with RCC. Affected patients in high-risk families often develop multiple, bilateral renal tumors. These include patients with von Hippel- Lindau (VHL) disease (an inherited cancer syndrome in which 40% of the affected patients will develop RCC) ( 6 ) , patients with a form of RCC termed hereditary papillary renal carcinoma (HPRC) ( 7 ) , and patients with tuberous sclerosis ( 8 , 9 ) . The genes underlying each of these diseases have been cloned and germline mutations in affected patients have been identified ( Table 1 ).