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

使用大肠杆菌 MutS 蛋白和分解酶检测基因突变的新方法

• 批准号: 12671256
• 负责人: SHITOH Kazuhisa
• 金额: $ 2.18万
• 依托单位: JICHI MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671256/
• 关键词: E.coli Muts; Mismatch repair genes; Hereditary nonpolyposis colorectal carcinoma (HNPCC); hMLH1; hMSH2; Japanese clinical criteria; hMLH1 methylation; BRAF; HNPCC; Japan clinical criteria; マイクロサテライト不安定性; 大腸菌Mut S蛋白

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.

我们研究了如何提高大肠杆菌Mut和解离酶基因突变的检测效率。同时分析了452例大肠癌病例，其中69例符合日本临床诊断标准，106例符合Bethesda指南，以评价HNPCC（hereditary nonpolyposis colorectal carcinoma，遗传性非息肉病性大肠癌）较好的检测方法。结果，日本临床标准A适用于选择病例进行基因突变分析。我们认为，发病年龄小于50岁对筛查也很重要。对MSI（微卫星不稳定性）表型的病例进行TGF β RII突变分析和hMLH1和hMSH2免疫组化染色有助于选择应进行生殖系突变检测的病例。

项目成果

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

Koinuma K、Shitoh K、Miyakura Y、Furukawa T、Yamashita Y、Ota J、Ohki R、Choi YL、Wada T、Konishi F、Nagai H、Mano H：“BRAF 突变与散发性结直肠癌中广泛的 hMLM1 启动子甲基化有关

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)

Shitoh K、Furukawa T、Kojima M、Konishi F、Miyaki M、Tsukamoto T、Nagai H：“具有微卫星不稳定性的非家族性结直肠癌中 β-catenin-Tcf 信号通路的频繁激活。”基因、染色体与癌症 30。 32-37 (2001)

Kazuhisa Shito 他: "Microsatellite Instability as a Marker in Predicting Metachronous Multiple Colorectal Carcinomas after Surgery"Dis Colon Rectum. 45. 329-333 (2002)

Kazuhisa Shito 等人：“微卫星不稳定性作为手术后预测异时性多发性结直肠癌的标志物”Dis Colon ectum。 45. 329-333 (2002)

Taiji Furukawa他: "Evaluation of screening strategy for detecting hereditary nonopolyposis colorectal carcinoma."Cancer. 94(4). 911-920 (2002)

Taiji Furukawa 等人：“遗传性非息肉病性结直肠癌筛查策略的评估”，癌症 94(4) (2002)。

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)

Furukawa T、Konishi F、Shitoh K、Tsukamoto T、Nagai H：“遗传性非息肉病性结直肠癌病例中具有微卫星不稳定表型的早期小肠腺癌。”Int Colorectal Dis。