Hegde Madhuri R, Roa Benjamin B
Emory University, Atlanta, Georgia, USA.
Curr Protoc Hum Genet. 2009 Apr;Chapter 10:Unit 10.12. doi: 10.1002/0471142905.hg1012s61.
Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer syndrome that confers an elevated risk of early-onset colorectal cancer (CRC) and increased lifetime risk for other cancers of the endometrium, stomach, small intestine, hepatobiliary system, kidney, ureter, and ovary. HNPCC accounts for up to 5% of all CRC, making it the most common hereditary colorectal cancer syndrome. Germline mutations in methyl-directed mismatch repair (MMR) genes give rise to microsatellite instability (MSI) in tumor DNA. HNPCC is most often associated with mutations in the MLH1 gene on 3p21, the MSH2 gene on 2p21, and to a lesser extent MSH6 on 2p16. This unit presents a comprehensive molecular and genetic screening strategy for HNPCC mutations in the MLH1, MSH2, and MSH6 genes, including analysis of MSI, mutation scanning by denaturing high-pressure liquid chromatography (DHPLC), and DNA sequencing analysis.
遗传性非息肉病性结直肠癌（HNPCC）是一种常染色体显性癌症综合征，会增加早发性结直肠癌（CRC）的发病风险，并提高患子宫内膜癌、胃癌、小肠癌、肝胆系统癌、肾癌、输尿管癌和卵巢癌等其他癌症的终生风险。HNPCC占所有CRC病例的5%，是最常见的遗传性结直肠癌综合征。甲基定向错配修复（MMR）基因的种系突变会导致肿瘤DNA出现微卫星不稳定性（MSI）。HNPCC最常与3p21上的MLH1基因、2p21上的MSH2基因以及2p16上的MSH6基因的突变相关。本单元介绍了一种针对MLH1、MSH2和MSH6基因中HNPCC突变的全面分子和基因筛查策略，包括MSI分析、变性高压液相色谱法（DHPLC）进行突变扫描以及DNA测序分析。
