[Genetic analysis of adenomatous polyposis coli: analysis of alterations of oncogenes and tumor suppressor genes in colorectal tumors].
Adenomatous polyposis coli (APC) is a genetic disorder transmitted as an autosomal dominant trait. This syndrome is characterized by the development of numerous polyps during the first 20-30 years of life and classified into two phenotypes according to the number of polyps: the profuse and sparse types. If left untreated, most or all affected individuals are at a high risk of developing adenocarcinoma by as early as 40 years of age. Therefore, comparison of APC adenocarcinomas with non-polyposis colorectal carcinomas (NPCC) was thought to be useful for understanding genetically determined carcinogenesis. I investigated gene alterations in specimens obtained from 53 APC patients, of which 16 represented the profuse type and the others the sparse type, and from 15 NPCC patients. The results are summarized as follows: 1) K-ras gene mutations were detected more frequently in the profuse-type adenomas (43%) than in the sparse ones (14%) (p less than 0.05). 2) Loss of heterozygosity on the long arm of chromosome 5(5q), 18(18q) and the short arm of chromosome 17(17p) in the profuse-type adenomas was observed more frequently (22%) than in the sparse ones (7.3%) (p less than 0.05). 3) No significant differences were observed between APC adenocarcinomas and NPCCs regarding the allelic deletions on 5q, 17p and 18q in these tumors. 4) The alteration of the DCC gene, which is known to be involved in the formation of NPCC, was frequently detected in the APC adenocarcinomas, suggesting that similar genetic events are involved in the oncogenesis of adenocarcinomas from APC and NPCC.
Toshitani
K
K
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka.
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002887:Chromosomes, Human, Pair 18; D002895:Chromosomes, Human, Pair 5; D005784:Gene Amplification; D016163:Genes, DCC / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation