| Project/Area Number |
02670144
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science. |
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Principal Investigator |
MIYAKI Michiko Dept. Tumor Biochemistry, the Tokyo Metropolitan Institute of Medical Science Chief, 腫瘍生化学, 研究員 (20085624)
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| Co-Investigator(Kenkyū-buntansha) |
YANOSHITA Rei Dept. Tumor Biochemistry, the Tokyo Metropolitan Institute of Medical Science Ch, 腫瘍生化学, 研究員 (00224915)
TANAKA Kiyoko Dept. Tumor Biochemistry, the Tokyo Metropolitan Institute of Medical Science Ch, 腫瘍生化学, 研究員 (40124474)
関 まどか 東京都臨床研, 腫瘍生化学, 研究員 (80226638)
岡本 美恵子 東京都臨床研, 腫瘍生化学, 研究員 (80152354)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | DNA Diagnosis / Colorectal Adenomas / Colorectal Carcinomas / Tumor Suppressor Genes / Loss of Heterozygosity / K-ras mutation |
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| Research Abstract |
Loss of heterozygosity (IDH) and Kras mutation were analyzed in colorectal polygas and invasive carcinomas from FAP and non-FAP patients with distinct histopathological types.
LOH, being less than 2% in isoderate adenomas, was detected on chromosome 5q(20%) in severe adenomas, on 5q(26%) and 17p(38%) in intramacosal carcinomas, and on 5q(52%), 17p(56%), 18(46%), and 22q(33%) in invasive carcinomas from FAP patients. LOH on chromosome 5q occurred most frequently in the region close to the APC gene both in adenomas and carcinomas, and a loss of normal allele of the APC gene was demonstrated in 3 cases. Kras mutation markedly increased in the step of development from moderate (11%) to severe (36%) adenomas. Similar frequencies of genetic changes were observed in colorectal adenomas and carcinomas from non-FAP patients. Mutation of p53 gene was detected in high frequency in intramucosal carcinomas and invasive carcinomas from both FAP and non-FAP.
These results suggest the following mechanisms for the development of colon tumors in FAP patients : 1) The heterozygous mutant/wild-type condition at the APC gene causes formation of mild or moderate adenoma, 2) the loss of normal allele in the APC gene leads to a change from moderate to severe adenoma, 3) LOH on chromosome 17p and mutation in p53 gene contribute to the conversion of adenoma to intramucosal carcinoma, and 4) LOH on other chromosomes, such as 18 and 22q, are involved in the progression of intramucosal carcinoma to invasive carcinoma. 5) Kras mutation may also affect the development of moderate to severe adenoma.
These data indicate that the analysis of LOH and p53 mutation may be helpful in the diagnosis of colorectal tumors, which has previously been done only by histopathological methods.
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