MUTATIONAL STATE OF VON-HIPPEL-LINDAU AND ADENOMATOUS POLYPOSIS-COLI GENES IN RENAL TUMORS

Genetic alterations of the von Hippel-Lindau (VHL) tumor suppressor ge ne and the adenomatous polyposis coli (APC) gene in renal tumors were examined by PCR-SSCP analysis and direct sequencing. Tissues from 58 p rimary sporadic human renal cell tumors (49 clear-cell carcinomas, 6 n on-clear-cell carcinomas and 3 oncocytomas) from Japanese patients wer e used in this study. Somatic VHL mutations were detected in 26 (53%) of the clear-cell carcinomas, although no mutations in this gene were observed in any nonclear-cell carcinomas or oncocytomas. The frequency of mutations did not correlate with histological grade, clinical stag e or any of several other clinical factors examined. No differences in the frequency of VHL mutations or in the exons where mutations occurr ed within the gene were evident when we compared our results with thos e reported for American patients. However, frameshifts were more commo n in our Japanese panel of tumors than in American cases, where single -point mutations appear to be more frequent. No APC gene mutation was detected in any of our samples, These results indicate that VHL gene m utations are related to the carcinogenesis of the clear-cell type of p rimary renal cell carcinomas, whereas alteration of the APC gene is no t involved in the pathogenesis of this cancer.