1999 Fiscal Year Final Research Report Summary
Elucidation of carcinogenic mechanisms in ulcerative colitis
| Project/Area Number |
10671160
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | The Univ. of Tokyo |
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Principal Investigator |
SHINOZAKI Masaru The University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (10312315)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAMURA Yutaka The University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (80301109)
WATANABE Toshiaki The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部・附属病院, 助教授 (80210920)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Ulcerative colitis / Dysplasia / Microsatellite instability / APC / K-ras |
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| Research Abstract |
The status of genetic alterations in ulcerative colitis (UC)-associated neoplasia (UCAN) was investigated focusing on microsatellite instability (MSI) which is shown in a certain fraction of colorectal carcinomas, and adenomatous polyposis coli (APC) gene and K-ras gene, whose mutations occur in the early stage of sporadic colorectal tumorigenesis. Thirty-one UCAN from 15 UC patients who had undergone colorectal resection at our institution were investigated. There were 8 lesions of invasive carcinoma, 15 high-grade dysplasia (HGD) and 8 low-grade dysplasia (LGD). DNA was extracted from each neoplastic lesion and corresponding non-neoplastic tissue by microdissection method. MSI status at 9 microsatellite loci, loss of heterozygosity (LOH) at APC locus, and K-ras codon 12 point mutation were examined. As for MSI, 4/31 (13%) UCAN (carcinoma : 1/8 (13%). HGD : 2/15 (13%). LGD : 1/8 (13%) were MSI-high (3 or more unstable loci) and 12/31 (39%) UCAN (carcinoma : 3/8 (38%), HGD : 6/15 (40%), LGD : 3/8 (38%) were MSI-low (1 or 2 unstable loci). LOH at APC locus was not found in 9 UCAN from 6 informative (heterozygous) cases. K-ras mutation rate of UCAN was 3/31 (9.7%) (carcinoma : 2/8 (25%), HGD : 1/15 (7%) and LGD : 0/8). MSI is relatively common in UCAN and is present at the early stage of tumorigenesis of UCAN, and the involvement of genetic alterations of APC gene and K-ras gene is small. MSI may act as one of the mechanisms for the increased neoplastic risk in UC, and UCAN may develop through other carcinogenic pathway than sporadic carcinomas.
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