Allele Loss and Kras Mutation Involved in the Development of Colorectal Tumors in Patients with Familial Adenomatous Polyposis

To investigate the mechanism of colon carcinogenesis, the loss of heterozygosity and Kras mutation were analyzed in 24 advanced FAP carcinomas, 20 advanced non-FAP carcinomas, and 111 FAP polyps with distinct histopathological dysplasia. Allele loss was observed in advanced FAP carcinomas most frequently on chromosome 5q (38%), 17p(57%), 18(36%) and 22q(35%). Non-FAP carcinomas exhibited allele losses similar to those in the FAP carcinomas. The frequency of allele loss in polyps from FAP patients was low, but it was higher in more advanced polyps; the loss was observed on chromosome 5q (24%) in severe adenomas, and on chromosome 5q (25%) and 17p(30%) in intramucosal early carcinomas. Kras mutations were detected in 50% of the advanced FAP carcinomas. The mutation frequency in polyps was lower than that in advanced carcinomas, the frequency increasing with polyp size. The present results suggest, in addition to the FAP gene on chromosome 5q, a significant role of cumulative changes in multiple tumor suppressor genes and the Kras gene during the development of colon tumors.