Analysis of microsatellite instability in sporadic parathyroid adenomas.
Analysis of microsatellite instability in sporadic parathyroid adenomas.
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DOI：
10.1210/jc.2002-021455
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发表时间：
2003-03
期刊：
影响因子：
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通讯作者：
S. Mallya;James J. Gallagher;A. Arnold
中科院分区：
文献类型：
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作者：
S. Mallya;James J. Gallagher;A. Arnold
微卫星不稳定性（MSI）是人类肿瘤发生中与DNA错配修复缺陷（MMR）相关的基因组不稳定性形式。最近的报道表明MSI在散发性甲状旁腺腺瘤发病机制中的作用。然而，由于样本量小和/或缺乏全基因组MSI的系统分析，这些研究没有提供确凿的证据表明MMR缺陷在甲状旁腺肿瘤中很常见。为了进一步研究MSI是否在甲状旁腺肿瘤发生中发挥重要作用，我们使用一组由5个微卫星DNA标记物组成的小组分析了49个散发性甲状旁腺腺瘤的MSI，该标记物已被NCI研讨会推荐用于灵敏检测MSI，并在其他肿瘤类型中得到验证。这些微卫星位点通过PCR使用荧光标记的引物从49个样本的模板肿瘤DNA和匹配的正常DNA分离自相同患者的外周血白细胞进行扩增。49个肿瘤中没有一个在NCI标记物组的任何分析位点显示MSI的证据。这些观察结果强烈表明，缺陷的DNA MMR起着次要的作用，如果有的话，在散发性甲状旁腺腺瘤的发病机制。
Microsatellite instability (MSI) is the form of genomic instability associated with defective DNA mismatch repair (MMR) in human tumorigenesis. Recent reports have suggested a role for MSI in the pathogenesis of sporadic parathyroid adenomas. However, because of their small sample sizes and/or lack of systematic analysis of genome-wide MSI, these studies have not provided conclusive evidence that MMR defects are a common occurrence in parathyroid neoplasia. To further investigate whether MSI plays an important role in parathyroid tumorigenesis, we analyzed 49 sporadic parathyroid adenomas for MSI using a panel of 5 microsatellite DNA markers that has been recommended for sensitive detection of MSI by the NCI Workshop and validated in other tumor types. These microsatellite loci were amplified by PCR using fluorescent-labeled primers from the 49 samples of template tumor DNA and matching normal DNA isolated from the same patients' peripheral blood leukocytes. None of the 49 tumors showed evidence of MSI at any of the analyzed loci of the NCI marker panel. These observations strongly suggest that defective DNA MMR plays a minor role, if any, in the pathogenesis of sporadic parathyroid adenomas.