Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis

Loss of heterozygosity (LOH) and K-ras mutation were analyzed in 111 colorectal polyps and 26 invasive carcinomas from 40 patients with familial adenomatous polyposis of distinct histopathological types. LOH, being less than 2% in moderate adenomas, was detected on chromosome 5q (20%) in severe aden...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1990-11, Vol.50 (22), p.7166-7173
Main Authors: Miyaki, M, Seki, M, Okamoto, M, Yamanaka, A, Maeda, Y, Tanaka, K, Kikuchi, R, Iwama, T, Ikeuchi, T, Tonomura, A
Format: Article
Language:English
Subjects:
Adenomatous Polyposis Coli - genetics
Adenomatous Polyposis Coli - pathology
Chromosome Mapping
Chromosomes, Human, Pair 17
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 22
Chromosomes, Human, Pair 5
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
DNA Probes
DNA, Neoplasm - genetics
Heterozygote
Humans
Polymorphism, Restriction Fragment Length
Proto-Oncogene Proteins p21(ras) - genetics
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Summary:Loss of heterozygosity (LOH) and K-ras mutation were analyzed in 111 colorectal polyps and 26 invasive carcinomas from 40 patients with familial adenomatous polyposis of distinct histopathological types. LOH, being less than 2% in moderate adenomas, was detected on chromosome 5q (20%) in severe adenomas, on 5q (26%) and 17p (38%) in intramucosal carcinomas, and on 5q (52%), 17p (56%), 18 (46%), and 22q (33%) in invasive carcinomas. LOH on chromosome 5q occurred most frequently in the region close to the APC gene both in adenomas and carcinomas, and a loss of the normal allele of the APC gene was demonstrated in 3 cases. K-ras mutation markedly increased in the step of development from moderate (11%) to severe (36%) adenomas. These results suggest the following mechanisms for the development of colon tumors in patients with familial adenomatous polyposis: (a) the heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma; (b) the loss of the normal allele in the APC gene leads to a change from moderate to severe adenoma; (c) LOH on chromosome 17p contributes to the conversion of adenoma to intramucosal carcinoma; (d) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma; and (e) K-ras mutation may also affect the development of moderate to severe adenoma.
ISSN:0008-5472