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首页> 外文期刊>The Journal of molecular diagnostics: JMD >Analysis of hMLH1 and hMSH2 gene dosage alterations in hereditary nonpolyposis colorectal cancer patients by novel methods.
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Analysis of hMLH1 and hMSH2 gene dosage alterations in hereditary nonpolyposis colorectal cancer patients by novel methods.

机译：通过新方法分析遗传性非息肉病性大肠癌患者的hMLH1和hMSH2基因剂量变化。

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A significant fraction of hereditary nonpolyposis colorectal cancer cases with defective mismatch repair (ie, Lynch syndrome) have large genomic deletions or duplications in the mismatch repair genes, hMLH1 and hMSH2, which can be challenging to detect by traditional methods. For this study, we developed and validated a novel Southern blot analysis method that allows for ascertainment of the extent of the dosage alterations on an exon-by-exon basis and compared this method to a second novel technique, multiplex ligation-dependent probe amplification (MLPA). From a total of 254 patients referred for Lynch syndrome testing, 20 of the 118 MLH1 cases and 42 of the 136 MSH2 cases had large genomic alterations, as detected by Southern blot. MLPA and Southern blot results were concordant with the exception of three major discrepancies: one because of a lack of MLPA probes for the region altered, another because of a point mutation near the MLPA probe ligation site, and another that was unexplained. Compared to Southern blot, MLPA has a shorter turn-around time, the analysis is less costly, less time-consuming, and less labor-intensive, and results are generally clear and unambiguous. However, concerns with MLPA include the presence of false-negatives and -positives because of positioning of probes and DNA variants near the probe ligation site. Overall, both Southern blot and MLPA provide important tools for the complete evaluation of patients with Lynch syndrome.
机译：错配修复缺陷（即Lynch综合征）的遗传性非息肉病性大肠直肠癌病例中，很大一部分在错配修复基因hMLH1和hMSH2中存在大量的基因组缺失或重复，这对传统方法很难检测。在这项研究中，我们开发并验证了一种新颖的Southern印迹分析方法，该方法可确定每个外显子剂量变化的程度，并将该方法与第二种新技术进行比较，即多重连接依赖性探针扩增（ MLPA）。通过Southern blot检测，在总共254名接受Lynch综合征检测的患者中，118例MLH1病例中有20例和136 MSH2病例中有42例具有较大的基因组改变。 MLPA和Southern blot结果与以下三个主要差异一致：一个是因为缺少该区域改变的MLPA探针，另一个是因为MLPA探针连接位点附近的点突变，另一个是无法解释的。与Southern blot相比，MLPA的周转时间更短，分析成本更低，耗时更少，劳动强度更低，并且结果通常是清晰明确的。然而，由于探针和DNA变体在探针连接位点附近的定位，对MLPA的关注包括假阴性和假阳性的存在。总体而言，Southern blot和MLPA都为全面评估Lynch综合征患者提供了重要的工具。

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