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 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.
Miyaki
M
M
Department of Biochemistry, Tokyo Metropolitan Institute of Medical Science, Japan.
Seki
M
M
Okamoto
M
M
Yamanaka
A
A
Maeda
Y
Y
Tanaka
K
K
Kikuchi
R
R
Iwama
T
T
Ikeuchi
T
T
Tonomura
A
A
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D002887:Chromosomes, Human, Pair 18; D002892:Chromosomes, Human, Pair 22; D002895:Chromosomes, Human, Pair 5; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D015342:DNA Probes; D004273:DNA, Neoplasm / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D012150:Polymorphism, Restriction Fragment Length; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
D015342:DNA Probes; D004273:DNA, Neoplasm; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)