Loss of constitutional heterozygosity in colon carcinoma from patients with familial polyposis coli.

Recent studies have suggested a critical role of specific gene loss in several embryonic tumours and certain adult cancers. In retinoblastoma, hemizygosity or homozygosity of a recessive mutant allele results in the loss of normal gene product, and this seems to cause the manifestation of the disorder. Familial polyposis coli (FPC) is a human autosomal dominant trait characterized by numerous adenomatous polyps of the colon and rectum, and a high incidence of colon carcinoma. Karyotype analyses have failed to detect specific deletion or translocation. We report the use of polymorphic DNA markers to look for the somatic loss of heterozygosity at specific loci. Investigation of 38 tumours from 25 FPC patients, and 20 sporadic colon carcinomas from 19 patients, revealed frequent occurrence of allele loss on chromosome 22, with some additional losses on chromosomes 5, 6, 12q and 15. The FPC gene-linked DNA probe C11p11 also detected frequent allele loss in both familial and sporadic colon carcinomas but not in benign adenomas. These results suggest the possible involvement of more than one chromosomal locus in the development of familial and sporadic colon carcinomas.