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首页> 外文期刊>Gastroenterology >It is time to get serious about diagnosing Lynch syndrome (hereditary nonpolyposis colorectal cancer with defective DNA mismatch repair) in the general population.
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It is time to get serious about diagnosing Lynch syndrome (hereditary nonpolyposis colorectal cancer with defective DNA mismatch repair) in the general population.

机译：现在是时候在一般人群中认真诊断Lynch综合征（遗传性非息肉病性结肠直肠癌，DNA错配修复缺陷）了。

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Hereditary nonpolyposis colorectal cancer (HNPCC), also called Lynch syndrome after Henry T. Lynch, MD, a pioneer in the field, is an autosomal dominant hereditary cancer syndrome, which accounts for upwards of 3% of all colorectal cancers, and is associated with an increased risk of endometrial, ovarian, and other extra-colonic cancers. Colorectal cancer can be averted in Lynch syndrome by early an intensive surveillance, and has been shown to be cost-effective. The syndrome originally was defined in clinical terms by the stringent Amsterdam criteria, although over time more relaxed clinical definitions have been suggested, culminating in the recently published revised Bethesda guidelines. Many cases of clinically defined Lynch syndrome are caused by a germline mutation in one of a set of genes responsible for DNA mismatch repair, with most of the disease causing mutations occurring in either MSH2 or MLH1, a smaller number in MSH6, and a few in PMS2. Deficient mismatch repair, manifest as high-frequency microsatellite instability (MSI-H), can be demonstrated in DNA from upwards of 95% Lynch-related colorectal cancers, and nearly all of the tumors also will demonstrate a loss of expression of one or more of the protein products of the DNA mismatch repair genes by immunohistochemistry (IHC). Because 10%-20%of sporadic colorectal cancers are also MSI-H, due to somatic inactivation of MLH1 via promoter methylation,the finding of MSI-H, or loss of MLH1 expression in a tumor, is suggestive, but is not diagnostic of Lynch syndrome. Lack of MLH1 promoter methylation and/or lack of a somatic activating mutation in the proto-oncogene BRAF (V600E) in Lynch-related cancers, however, can distinguish most of these from sporadic MSI-H cancers with a high degree of accuracy.
机译：遗传性非息肉病性结直肠癌（HNPCC），在该领域的先驱者Henry T. Lynch，MD后也称为Lynch综合征，是常染色体显性遗传性癌症综合征，占所有结直肠癌的3％以上，并且与子宫内膜癌，卵巢癌和其他结肠外癌的风险增加。大肠癌可以通过早期的强化监视来避免Lynch综合征，并且已被证明具有成本效益。该综合征最初是由严格的阿姆斯特丹标准以临床术语定义的，尽管随着时间的推移，人们提出了更为宽松的临床定义，最终以最近发布的修订后的Bethesda指南告终。许多临床上定义为Lynch综合征的病例是由负责DNA错配修复的一组基因中的种系突变引起的，其中大多数疾病导致MSH2或MLH1发生突变，MSH6发生的突变较少， PMS2。错配修复不足，表现为高频微卫星不稳定性（MSI-H），可从超过95％的林奇相关结直肠癌的DNA中证实，几乎所有肿瘤也将表现出一种或多种表达的丧失。 DNA错配修复基因的蛋白质产物通过免疫组织化学（IHC）进行鉴定。由于10％-20％的散发性结直肠癌也是MSI-H，由于通过启动子甲基化使MLH1发生体细胞失活，因此发现MSI-H或MLH1表达缺失在肿瘤中是提示性的，但不能诊断为林奇综合症。在林奇相关的癌症中，原癌基因BRAF（V600E）中缺少MLH1启动子甲基化和/或缺乏体细胞激活突变，可以将这些大多数与散发性MSI-H癌症区分开来。

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