A new method for detection of gene mutations using both E.coli MutS protein and resolvase

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671256
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: JICHI MEDICAL SCHOOL
• Principal Investigator: SHITOH Kazuhisa Jichi Medical School of Medicine, Assistant professor, 医学部, 助手 (90285792)
• Co-Investigator(Kenkyū-buntansha): TSUKAMOTO Toshihiko Kitasato University, Assistant Professor, 薬学部, 助教授 (10236862)
• Project Period (FY): 2000 – 2003
• Keywords: E.coli Muts / Mismatch repair genes / Hereditary nonpolyposis colorectal carcinoma (HNPCC) / hMLH1 / hMSH2 / Japanese clinical criteria / hMLH1 methylation / BRAF

Research Abstract

We have investigated to upgrade the detection efficiency for gene mutation modifying both E.coli Muts and resolvase. Together with it, we analyzed 452 colorectal carcinoma cases, of which 69 cases fulfilled the Japanese clinical criteria and 106 fulfilled the Bethesda guidelines to evaluate the better method for detection of HNPCC (hereditary nonpolyposis colorectal carcinoma). As results, Japanese clinical criteria A are suitable for selecting cases to analyze for gene mutations. And we suggested that an age at onset younger than 50 years was also important for screening. Analyzing TGF β RII mutations and immunohistochemical staining of hMLH1 and hMSH2 for cases with MSI (microsatellite instability) phenotype are useful for selecting cases who should be tested for germline mutations.

Research Products

• [Publications] Taiji Furukawa他: "Evaluation of screening strategy for detecting hereditary nonopolyposis colorectal carcinoma."Cancer. 94(4). 911-920 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kazuhiusa Shitoh他: "Microsatellite Instability as a Marker in Predicting Metachronous Multiple Colorectal Carcinomas after Surgery"Dis Colon Rectum. 45. 329-333 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Taiji Furukawa他: "An early stage small bowel adenocarcinoma with microsatellite instability phenotype in a case of hereditary nonpolyposis colorectal cancer"Int J Colorectal Dis. 18. 267-270 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Koji Koinuma他: "Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas"Int J Cancer. 108. 237-242 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Taiji Furukawa他: "Densely methylated hMLH1 promoter correlates with decreased mRNA expression in sporadic colorectal cancers"Genes Chromosomes Cancer. 35. 1-10 (2002)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shitoh K, Furukawa T, Kojima M, Konishi F, Miyaki M, Tsukamoto T, Nagai H: "Frequent activation of the β-catenin-Tcf signaling pathway in nonfamilial colorectal carcinomas with microsatellite instability."Genes, Chromosomes & Cancer. 30. 32-37 (2001)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Furukawa T, Konishi F, Masubuchi S, Shitoh K, Nagai H, Tsukamoto T: "Densely methylated MLH1 promoter correlates with decreased mRNA expression in sporadic colorectal cancers."Genes, Chromosomes & Cancer. 35. 1-10 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Furukawa T, Konishi F, Shitoh K, Kojima M, Nagai H, Tsukamoto T: "Evaluation of screening strategy for detecting hereditary nonpolyposis colorectal carcinoma."Cancer. 94. 911-920 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Shitoh K, Konishi F, Miyakura Y, Togashi K, Okamoto T, Nagai H: "Microsatellite instability as a marker in predicting metachronous multiple colorectal carcinomas after surgery."Dis.Colon Rectum. 45(3). 329-333 (2002)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Furukawa T, Konishi F, Shitoh K, Tsukamoto T, Nagai H: "An early stage small bowel adenocarcinoma with microsatellite instability phenotype in a case of hereditary nonpolyposis colorectal cancer."Int Colorectal Dis. 18. 267-270 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Koinuma K, Shitoh K, Miyakura Y, Furukawa T, Yamashita Y, Ota J, Ohki R, Choi YL, Wada T, Konishi F, Nagai H, Mano H: "Mutations of BRAF are associated with extensive hMLM1 promoter methylation in sporadic colorectal carcinoma."Int J Cancer. 108. 237-242 (2004)
  • Description: 「研究成果報告書概要(欧文)」より