Elucidation of carcinogenic mechanisms in ulcerative colitis

• Project/Area Number: 10671160
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: The Univ. of Tokyo
• Principal Investigator: SHINOZAKI Masaru (1999) The University of Tokyo, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (10312315); 佐々木 愼 (1998) 東京大学, 医学部・附属病院, 助手 (00292946)
• 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) ; 松田 圭二 東京大学, 医学部・附属病院, 助手 ; 古川 洋一 東京大学, 医科学・研究所, 助手 (20272560) ; 正木 忠彦 東京大学, 医学部・附属病院, 助手 (30238894)
• Project Period (FY): 1998 – 1999
• Project Status: Completed (Fiscal Year 1999)
• Budget Amount: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 1999: ¥400,000 (Direct Cost: ¥400,000); Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: Ulcerative colitis / Dysplasia / Microsatellite instability / APC / K-ras / dysplasia / RER

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.

Research Products

• [Publications] Naoyuki Umetani, et al.: "Genetic Alteration in Ulcerative colitis-associated Neoplasia Focusing on APC, K-ras Gene and Microsatellite instability"Jpn. J. Cancer Res.. 90. 1081-1087 (1999)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Naoyuki Umetani et al.: "Genetic Alteration in Ulcerative Calitx-associated Neoplasis Focusing an APC, K-ras gene and Microsatellite Instability"Jpn. J. Cancer Res.. 90. 1081-1087 (1999)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Naoyuki Umetani et al.: "Genetic Alteration in Ulcerative colitis-associated Neoplasia Focusing on APC,K-ras Gene and Microsatellite instability"Jpn. J. Cancer Res.. 90. 1081-1087 (1999)