The Role of MGMT Testing in Clinical Practice A Report of the Association for Molecular Pathology
The Role of MGMT Testing in Clinical Practice A Report of the Association for Molecular Pathology
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DOI：
10.1016/j.jmoldx.2013.05.011
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发表时间：
2013-09-01
影响因子：
4.1
通讯作者：
Lee, Eudocia Q.
中科院分区：
文献类型：
--
作者：
Cankovic, Milena;Nikiforova, Marina N.;Lee, Eudocia Q.
现代分子技术的最新进展允许检查和测量与癌症相关的基因组变化。用于评估诊断、预后或预测标记的分子测试数量预计将会增加。近年来，O-6-甲基鸟嘌呤-DNA 甲基转移酶 (MGMT) 启动子甲基化已被牢固确立为神经胶质瘤患者的生物标志物，用于临床试验和常规临床管理。同样，分子标记，例如 1p/19q 杂合性丢失 (LOH) 已经证明在少突胶质细胞肿瘤治疗中具有临床实用性，其他分子标记可能很快就会显示出临床实用性。此外，我们还发现 MGMT、1p/19q LOH、异柠檬酸脱氢酶 (IDH) 突变和其他肿瘤特异性修饰之间存在非随机关联，这些关联可能会增强我们预测结果和治疗反应的能力。虽然病理学家面临着新的、更复杂的临床基因组测试要求，但临床医生也面临着来自分子病理学和基因组医学的越来越多的分子数据的挑战。病理学家和肿瘤学家都需要了解分子测试和测试结果的临床效用，包括周转时间问题及其对靶向治疗方案应用的影响。本综述总结了支持 MGMT 启动子甲基化测试以及临床定义的神经胶质瘤亚型中可能的其他分子测试的基本原理的现有数据。还讨论了用于评估 MGMT 甲基化状态的各种分子测试平台。
Recent advances in modern molecular technologies allow for the examination and measurement of cancer-related genomic changes. The number of molecular tests for evaluation of diagnostic, prognostic, or predictive markers is expected to increase. In recent years, O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation has been firmly established as a biomarker in patients diagnosed with gliomas, for both clinical trials and routine clinical management. Similarly, molecular markers, such as loss of heterozygosity (LOH) for 1p/19q have already demonstrated clinical utility in treatment of oligodendroglial tumors, and others might soon show clinical utility. Furthermore, nonrandom associations are being discovered among MGMT, 1p/19q LOH, isocitrate dehydrogenase (IDH) mutations, and other tumor-specific modifications that could possibly enhance our ability to predict outcome and response to therapy. While pathologists are facing new and more complicated requests for clinical genomic testing, clinicians are challenged with increasing numbers of molecular data coming from molecular pathology and genomic medicine. Both pathologists and oncologists need to understand the clinical utility of molecular tests and test results, including issues of turnaround time, and their impact on the application of targeted treatment regimens. This review summarizes the existing data that support the rationale for MGMT promoter methylation testing and possibly other molecular testing in clinically defined glioma subtypes. Various molecular testing platforms for evaluation of MGMT methylation status are also discussed.