Genetic testing is important in families with a history suggestive of hereditary non-polyposis colorectal cancer even if the Amsterdam criteria are not fulfilled
Genetic testing is important in families with a history suggestive of hereditary non-polyposis colorectal cancer even if the Amsterdam criteria are not fulfilled
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DOI：
10.1002/bjs.1800840228
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发表时间：
1997-02-01
影响因子：
9.6
通讯作者：
Bodmer, WF
中科院分区：
文献类型：
--
作者：
Beck, NE;Tomlinson, IPM;Bodmer, WF
背景临床筛查仍然是鉴定遗传性非息肉病性结直肠癌(HNPCC)家系的首选方法。由于需要统一诊断，特别是在多中心研究中，因此建立了一套最低限度的诊断标准，即“阿姆斯特丹标准”。现在已经知道HNPCC是由人类错配修复基因中的生殖系缺陷引起的，DNA预测测试是可能的。已知的错配修复基因hMSH2和hMLH1的缺陷占HNPCC家系突变的90%以上。方法对10个HNPCC家系进行家系鉴定，家系提示HNPCC(可能为显性遗传性HNPCC)，但不符合阿姆斯特丹标准。应用单链构象多态分析技术，对这10个家系的受累成员进行hMSH2和hMLH1基因的种系突变筛查。在这些基因中，有三个是错义的，一个是无义的，一个是移码的，一个是推测的剪接点突变。其中3个突变位于hMSH2，3个位于hMLH1。结论本研究表明，即使不符合阿姆斯特丹标准，所有有HNPCC家系提示的家系也应咨询遗传学家。了解基因携带者的状态可以进行有针对性的监测，并有可能进行可能治愈的早期手术干预。
Background Clinical screening is still the first-line approach to identification of families with hereditary non-polyposis colorectal cancer (HNPCC). The need for uniformity of diagnosis of the syndrome, particularly in multicentre studies, led to the establishment of a set of minimum diagnostic criteria, the 'Amsterdam criteria'. It is now known that HNPCC is caused by germline defects in the human mismatch repair genes and DNA predictive testing is possible. Defects in two of the known mismatch repair genes, namely hMSH2 and hMLH1, account for over 90 per cent of mutations found in HNPCC families.Methods Ten families were identified with pedigrees suggestive of HNPCC (that is with a possible dominant inheritance of HNPCC), but in which the Amsterdam criteria were not fulfilled. Using the technique of single-strand conformational polymorphism analysis, samples were screened from an affected member of each of these ten kindreds for germline mutations in the genes hMSH2 and hMLH1.Results Mutations were identified in six families. Of these, there were three missense, one nonsense, one frameshift and one putative splice-site mutation. Three of the mutations were in hMSH2 and three in hMLH1.Conclusion This study demonstrates that all families with a pedigree suggestive of HNPCC should be referred to a geneticist even if the Amsterdam criteria are not fulfilled. A knowledge of the gene carrier status enables targeted surveillance and the possibility of early surgical intervention that could be curative.