Tumor suppressor gene allelic loss in human renal cancers

It is now apparent that multiple genetic alterations, including oncogene activation and tumor suppressor gene inactivation, are necessary steps in carcinogenesis. We have studied this concept in renal cancers by looking at specific tumor suppressor genes implicated in several allelotyping studies. Primary, predominantly low stage renal tumors of varying grades and histologic subtypes were investigated for allelic loss of 3p, 17p and the p53 gene, the DCC gene and the Rb gene and its product. 3p loss occurred in 47% of tumors studied and was much more common in clear cell cancers (85%). 17p and p53 gene loss were relatively uncommon events with only 6 of 42 tumors demonstrating loss. None of the tumors with typical histologies had allelic loss of the DCC gene, though loss did occur in leiomyosarcoma and a collecting duct tumor. Allelic loss of the Rb gene occurred in one clear cell tumor, the leiomyosarcoma, and, interestingly, in both collecting duct tumors in this series. Allelic loss of the Rb gene was correlated with little or no RB protein expression as judged by immunohistochemistry. At all loci studied, allelic loss did not appear to correlate with tumor grade or stage. These results suggest that inactivation of the p53, Rb, and DCC genes by allelic loss are uncommon events in the early stages of renal carcinogenesis.