Clinical Neuropathology practice guide 5-2015: MGMT methylation pyrosequencing in glioblastoma: unresolved issues and open questions
Clinical Neuropathology practice guide 5-2015: MGMT methylation pyrosequencing in glioblastoma: unresolved issues and open questions
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DOI：
10.5414/np300904
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发表时间：
2015-09-01
影响因子：
1.1
通讯作者：
Preusser, Matthias
中科院分区：
文献类型：
--
作者：
Bienkowski, Michal;Berghoff, Anna S.;Preusser, Matthias
O 6-甲基鸟嘌呤-甲基转移酶（MGMT）启动子甲基化状态对新诊断的胶质母细胞瘤具有预后价值，在老年患者亚群中具有预测价值。因此，了解MGMT启动子甲基化状态对于临床决策非常重要。到目前为止，MGMT测试一直受到缺乏具有足够高分析性能的稳健测试的限制。最近，几个可用的焦磷酸测序协议之一已被证明是一个准确和强大的方法MGMT测试在内部和实验室间的环形试验。然而，在方法学问题、临界值定义和临床环境中的最佳使用方面仍存在一些不确定性。在这篇文章中，我们强调并讨论了其中几个开放的问题。主要未解决的问题是最相关的CpG位点的定义，以分析用于临床目的，并确定一个截止值的二分法定量MGMT焦磷酸测序结果为“MGMT甲基化”和“MGMT非甲基化”的患者亚组作为进一步治疗决策的基础。
O6-methylguanine-methyltransferase (MGMT) promoter methylation status has prognostic and, in the subpopulation of elderly patients, predictive value in newly diagnosed glioblastoma. Therefore, knowledge of the MGMT promoter methylation status is important for clinical decision-making. So far, MGMT testing has been limited by the lack of a robust test with sufficiently high analytical performance. Recently, one of several available pyrosequencing protocols has been shown to be an accurate and robust method for MGMT testing in an intra- and interlaboratory ring trial. However, some uncertainties remain with regard to methodological issues, cut-off definitions, and optimal use in the clinical setting. In this article, we highlight and discuss several of these open questions. The main unresolved issues are the definition of the most relevant CpG sites to analyze for clinical purposes and the determination of a cut-off value for dichotomization of quantitative MGMT pyrosequencing results into "MGMT methylated" and "MGMT un-methylated" patient subgroups as a basis for further treatment decisions.