Establishment and application to clinical diagnosis of convenient method for genomic instability in gastroenterological cancer.

胃肠道肿瘤基因组不稳定性便捷方法的建立及其在临床诊断中的应用

• 批准号: 07671430
• 负责人: TSUJITA Kazunori
• 金额: $ 1.47万
• 依托单位: TOHO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671430/
• 关键词: colorectal cancer; HNPCC; replication error; microsatellite instability; hMSH2; hMLH1; antibody; immunoblot; hMLH1; Anti body; Immunoblot; ゲノム不安定性; ミスマッチリペア-遺伝子; hMSH2抗体; hMLH1抗体

This study was supported by Grant-in Aid for Scientific Research (c) (2), PROJECT NUMBER was 07671430, TITLE : Establishment and application to clinical diagnosis of convenient method for genomic instability in gastroenterological cancer.We studied here RER and expression of hMSH2 and hMLH1 proteins by in 40 samples of colorectal cancer. Genomic DNA was extracted from tumor and normal tissues for determining RER with 8 microsatellite markers. Expression of hMSH2 and hMLH1 proteins in tumor and normal tissues was examined by immunoblot. The RER-positive phenotype was found in 6 (16%) of the 37 sporadic cases. hMLH1 protein in 2 of the 6 RER-positive tumor tissues, but not the normal tissues, was failed to be detected, indicating that the tumor tissues of the 2 patients had severe mutations in both alleles of hMLH1 gene. hMSH2 protein was detected in all samples. hMLH1 protein was undetectable in the 2 tumor tissues of the 6 RER-positive samples of sporadic colorectal cancer. The detection procedure employed here may have potential utility for determining the dysfunctional MMR gene as a primary screening.

本研究得到科学研究资助基金(c)(2)的支持，项目编号为07671430，标题：胃肠道癌症基因组不稳定性便捷方法的建立及其在临床诊断中的应用。我们在这里研究了RER和hMSH2的表达和 hMLH1 蛋白存在于 40 个结直肠癌样本中。从肿瘤和正常组织中提取基因组 DNA，用 8 个微卫星标记测定 RER。通过免疫印迹检测肿瘤和正常组织中hMSH2和hMLH1蛋白的表达。 37 例散发病例中，有 6 例（16%）发现 RER 阳性表型。 6例RER阳性肿瘤组织中有2例未能检测到hMLH1蛋白，而正常组织中未检测到hMLH1蛋白，表明2例患者的肿瘤组织中hMLH1基因的两个等位基因均存在严重突变。所有样品中均检测到 hMSH2 蛋白。 6例RER阳性散发性结直肠癌样本的2例肿瘤组织中未检测到hMLH1蛋白。这里采用的检测程序可能具有确定功能失调的 MMR 基因作为初步筛选的潜在用途。