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首页> 外文期刊>Oncogene >Dual role of LOH at MMR loci in hereditary non-polyposis colorectal cancer?
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Dual role of LOH at MMR loci in hereditary non-polyposis colorectal cancer?

机译：在遗传性非息肉性结直肠癌中，MMR基因座上的LOH有双重作用吗？

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hMLH1 and hMSH2 can be considered tumor suppressor genes, as both alleles must be inactivated in order to lose the mismatch repair (MMR) function. In this regard, it has been proposed that LOH at MMR loci is a common Knudson's second-hit mechanism in HNPCC patients. However, experimental evidence supporting this view is scarcely found in the literature. We have performed a comprehensive analysis of LOH in 45 HNPCC tumors carrying a germline alteration in MMR loci. Overall, we have detected LOH at MMR loci in 56% of the cases. However, up to 40% of the LOH events targeted the mutant allele, arguing against a second-hit role in these tumors. Interestingly, the age at diagnosis was significantly older in these patients. To explain this and previous data, we propose a dual role for LOH at MMR loci in HNPCC.
机译：hMLH1和hMSH2可以被认为是肿瘤抑制基因，因为两个等位基因都必须失活才能失去错配修复（MMR）功能。在这方面，已经提出在MMR基因座处的LOH是HNPCC患者中常见的克努森的第二击机制。但是，在文献中几乎找不到支持这种观点的实验证据。我们对携带MMR基因座种系改变的45例HNPCC肿瘤中的LOH进行了全面分析。总体而言，我们在56％的病例中在MMR位点检测到LOH。但是，高达40％的LOH事件以突变等位基因为靶点，这与这些肿瘤中的二次打击作用有关。有趣的是，这些患者的诊断年龄明显更高。为了解释此数据和以前的数据，我们提出了HNPCC中MMR基因座的LOH的双重作用。

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