Beck N E, Tomlinson I P, Homfray T, Frayling I, Hodgson S V, Harocopos C, Bodmer W F
Cancer Genetics and Immunology Laboratory, John Radeliffe Hospital, Headington, Oxford, Oxfordshire, UK.
Hum Genet. 1997 Feb;99(2):219-24. doi: 10.1007/s004390050343.
Hereditary non-polyposis colorectal cancer (HNPCC) is a clinical syndrome characterised by an inherited predisposition to early onset colorectal and uterine cancers and an increased incidence of other cancers. It is caused by germline defects in the human mismatch repair genes. Defects in two of the known mismatch repair genes (namely hMSH2 and hMLH1) account for over 90% of mutations found in HNPCC families. In this study we have identified 14 families that fulfilled the clinical criteria for HNPCC and screened the hMSH2 and hMLH1 genes for germline mutations using single-strand conformational polymorphism (SSCP) analysis and DNA sequencing. Seven mutations were identified. Of these, there were five frameshifts, one missense mutation and a further novel mutation that involved separate transition and transversion changes in successive amino acid residues. Three of the mutations were in hMSH2 and four in hMLH1. The identification of germ-line mutations in an HNPCC family enables targeted surveillance and the possibility of early curative intervention. SSCP is a simple and effective method for identifying most mutations in the human mismatch repair genes using DNA from fresh, frozen or archival material.
遗传性非息肉病性结直肠癌（HNPCC）是一种临床综合征，其特征为遗传易感性导致早发性结直肠癌和子宫癌，以及其他癌症的发病率增加。它由人类错配修复基因中的种系缺陷引起。在已知的错配修复基因中，两个基因（即hMSH2和hMLH1）的缺陷占HNPCC家族中发现的突变的90%以上。在本研究中，我们确定了14个符合HNPCC临床标准的家族，并使用单链构象多态性（SSCP）分析和DNA测序对hMSH2和hMLH1基因进行种系突变筛查。共鉴定出7个突变。其中，有5个移码突变、1个错义突变以及另一个新突变，该新突变涉及连续氨基酸残基的单独转换和颠换变化。3个突变位于hMSH2基因，4个位于hMLH1基因。在HNPCC家族中鉴定种系突变能够实现靶向监测以及早期治愈性干预的可能性。SSCP是一种使用新鲜、冷冻或存档材料的DNA鉴定人类错配修复基因中大多数突变的简单有效方法。
