[Genetic analysis of familial polyposis coli. Linkage analysis and loss of heterozygosity in colorectal tumors of FPC by RFLP analysis]

Abstract

Familial polyposis coli (FPC) is a genetic disorder, transmitted as an autosomal dominant trait, characterized by numerous colorectal adenomas. If untreated, most patients may develop colorectal adenocarcinomas. We investigated linkage between FPC and several DNA markers, and loss of heterozygosity in colorectal tumors by using RFLP analysis. We examined 15 pedigrees for linkage analysis and 31 FPC patients including 16 adenocarcinomas and 43 adenomas and 15 non-polyposis colorectal carcinomas (NPCC) for searching loss of heterozygosity. 1. Significant linkage was not observed with 26 polymorphic DNA probes. Maximum lod score of 0.301 at a recombination fraction of 0.0 was observed with the marker D5S71, which was reported to be tightly linked to the major gene for FPC in Caucasian. 2. Loss of heterozygosity was observed at the loci on 17 chromosomes in colorectal carcinomas from FPC patients, and on 6 chromosomes in NPCC. Thus, chromosomes in FPC patients may be unstable compared with those in patients with NPCC. 3. Frequent loss of heterozygosity in colorectal carcinomas from FPC patients was observed on chromosomes 5 (20%), 14 (22%), 17 (43%) and 22 (38%), and was also observed on chromosomes 5 (33%), 14 (38%), 17 (27%) and 22 (15%) in NPCC. These results suggest that tumor suppression genes may locate on these chromosomes. 4. Tumor suppression genes may play a role by dose dependent way.