Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors
Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors
复制标题
DOI：
10.1200/jco.2005.02.7227
复制
发表时间：
2006-01-10
影响因子：
45.3
通讯作者：
Hamelin, R
中科院分区：
文献类型：
--
作者：
Buhard, O;Cattaneo, F;Hamelin, R
目的：人胃肠道肿瘤中存在失活的DNA错配修复系统（MSI），具有独特的分子生物学和临床病理特征，预后良好。有证据表明，与非MSI肿瘤患者相比，MSI肿瘤的结直肠癌患者对辅助化疗的反应不同。最后，MSI状态的测定具有临床应用，可用于辅助诊断疑似遗传性病例。因此，越来越多的人认识到，MSI的检测应该在所有可能属于这种类型的人类癌症中系统地进行。我们最近描述了一种五重聚合酶链反应的五个单核苷酸重复序列，以建立人类肿瘤的MSI状态，并表明，这种测定是100%的敏感性和特异性。此外，这些标记在白色群体的生殖系DNA中是准单态的（即，欧亚起源的个体），并且可以用于肿瘤MSI测定，而不需要匹配该组中的正常DNA.Patients和Methods在这项研究中，我们分析了来自1，结果除2个Biaka俾格米人和1个San人的3个标记显示变异等位基因外，（3例[0.2%]），其余1，203例个体未显示变异大小的等位基因（1，055例[87.5%]），或仅一个（122例[10.1%]）或两个（26例[2.2%]）标记具有变异等位基因。所有60 MSI肿瘤调查显示至少有四个的5 markets.Conclusion不稳定，我们表明，肿瘤MSI状态可以确定使用五链反应的所有人群，而不需要匹配的正常DNA。
Purpose Human gastrointestinal tumors with inactivated DNA mismatch repair system (microsatellite instability [MSI] tumors) have distinct molecular and clinicopathologic profiles, and are associated with favorable prognosis. There is evidence suggesting that colorectal cancer patients with MSI tumors respond differently to adjuvant chemotherapy as compared with patients with non-MSI tumors. Finally, determination of the MSI status has clinical application for assisting in the diagnosis of suspected hereditary cases. It is thus becoming increasingly recognized that testing for MSI should be conducted systematically in all human cancers potentially of this type. We recently described a pentaplex polymerase chain reaction of five mononucleotide repeats to establish the MSI status of human tumors, and showed that this assay was 100% sensitive and specific. Moreover, these markers are quasi monomorphic in germline DNA of the white population (ie, individuals of Eurasian origin), and could be used for tumor MSI determination without the requirement for matching normal DNA in this group.Patients and Methods In this study, we analyzed a comparable panel of five mononudeotice markers in germline DNA from 1,206 individuals encompassing 55 different populations worldwide.Results With the exception of two Biaka Pygmies and one San individual for whom three markers showed variant alleles (three cases [0.2%]), the remaining 1,203 individuals showed no alleles of variant size (1,055 cases [87.5%]), or only one (122 cases [10.1 %]) or two (26 cases [2.2%]) markers with variant alleles. All 60 MSI tumors investigated display instability in at least four of the five markers.Conclusion We demonstrated that tumor MSI status can be determined using the pentaplex reaction for all human populations without the need for matching normal DNA.