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

Abstract

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.

Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor.

“…The recently identified neurofibromatosis 2 gene (Rouleau et al 1993;Trofatter et al 1993) is localized proximal to p300 at 22q12. Chromosomal deletions, including the 22q13 region, have been detected in certain types of colon cancer (Okamoto et al 1988) and gliomas (Jenkins et al 1989). Further analysis is under way to investigate a potential involvement of p300 in these cases.…”

Clonal allele loss in gastrointestinal cancers

“…In this study, it was found that of 31 colorectal cancers informative for chromosome 5 markers, six showed loss of heterozygosity at 5q with co-existing losses at chromosomes 17p and 18. As shown here and by others Okamoto et al, 1988) loss of heterozygosity in loci other than 18, 17p and 5q are only rarely involved in colonic cancers.…”

Refined mapping of eight cosmid markers on human chromosome 22

“…Loss of heterozygosity (LOH) on 22q has been reported in meningiomas, colorectal cancers, pheochromocytomas, and breast cancers, indicating the possible existence of tumor suppressor(s) on the chromosome arm (Dumanski et al, 1987;Okamoto et al, 1988;Tanaka et al, 1992;Shin et aI., 1993;Chert et al, 1991). Moreover, in the case of the DiGeorge syndrome (DGS), deletion of a certain region of 22qll is thought to be closely related with this disease (Driscoll et aI., 1992).…”