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Journal Article

Molecular Genetics of Renal Carcinogenesis

Cheryl Walker

The University of Texas MD Anderson Cancer Center, Science Park Research Division, Park Road 1C, Smithville, Texas 78957

Renal cell carcinoma (RCC) is the most common tumor of the adult kidney, accounting for 85% of renal neoplasms. RCC is heterogeneous in appearance, displaying diverse histologic and cytologic characteristics, with the clear cell variant being the most common. Individuals at high risk for this disease include persons with end-stage renal disease, those with hereditary predispositions such as von Hippel-Lindau syndrome (VHL) or tuberous sclerosis (TSC), and individuals with significant environment exposures such as smoking or analgesic abuse. Recently, several of the genetic targets for alterations involved in the development of human RCC have been identified. Solid RCC of the clear cell type is associated with alterations in the VHL tumor suppressor gene and hereditary papillary RCC is associated with alterations of the c-met protooncogene. In the rat, the most commonly seen tumors are of the non-clear cell type and it is the Tsc-2 tumor suppressor gene, rather than the VHL tumor suppressor gene, that appears to be the primary target for both spontaneous and carcinogen-induced mutations in these animals. These data suggest that different variants of RCC have distinct molecular etiologies and that there are species-specific determinants that modulate the involvement of specific tumor suppressor genes in RCC. Interestingly, many of the genes involved in RCC also play significant roles in kidney development. The Wilm's tumor suppressor gene, WT-1, and Pax-2 regulate the mesenchymal epithelial transition that occurs during nephrogenesis and both these genes exhibit altered expression patterns and/or are mutated in renal tumors. Other genes such as c-met and its ligand hepatocyte growth factor are also involved in normal development and tumorigenesis, suggesting that tumors arise as a result of altered functions that are reflective of events that occur during nephrogenesis.

Key Words: Renal cell carcinoma • von Hippel-Lindau syndrome • tuberous sclerosis • tumor suppressor gene • tumorigenesis

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Toxicologic Pathology, Vol. 26, No. 1, 113-120 (1998)
DOI: 10.1177/019262339802600113
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D. C. Wolf, L. M. Crosby, M. H. George, S. R. Kilburn, T. M. Moore, R. T. Miller, and A. B. Deangelo
Time- and Dose-Dependent Development of Potassium Bromate-Induced Tumors in Male Fischer 344 Rats
Toxicol Pathol, November 1, 1998; 26(6): 724 - 729.
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