高级别胶质瘤中o6 -甲基鸟嘌呤- dna甲基转移酶启动子甲基化状态分析

Hodan Ibrahim, A. Matter, A. Abdel-Aziz, F. Badr, E. Abdelmoemen
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摘要

背景:恶性胶质瘤中o6 -甲基鸟嘌呤- DNA甲基转移酶(MGMT)基因经常因启动子高甲基化而沉默,这已被确定为降低MGMT表达水平的表观遗传机制。在胶质瘤中,MGMT启动子超甲基化的状态及其与肿瘤进展的关系正在进行广泛的研究,以往的研究表明,这种表观遗传生物标志物与肿瘤表型和临床结局的关系的重要性存在矛盾的结果。因此,在我们的研究中,我们评估了表观遗传生物标志物的作用;高级别胶质瘤患者MGMT启动子甲基化状态,并将结果与肿瘤表型和临床结局相关。方法:该研究包括40例高级别胶质瘤患者,使用甲基化特异性PCR (MSP)评估MGMT启动子甲基化状态,并使用适当的统计方法将结果与临床组织病理学参数和生存率相关联。结果:MGMT启动子甲基化分析显示,65%的甲基化启动子患者和35%的未甲基化启动子患者与不同的治疗方式(手术、化疗或放疗)、复发率或总生存率没有显著的预后或预测意义。结论:MGMT启动子甲基化状态在指导高级别胶质瘤患者临床决策中的作用并不确定。需要进一步的研究来调查其在埃及高级别胶质瘤患者中作为表观遗传标记的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
O6-MethylGuanine-DNA Methyltransferase (MGMT) Promoter Methylation Status Analysis in High-Grade Gliomas
Background: The O6-methylguanine- DNA methyltransferase (MGMT) gene is frequently silenced by promoter hypermethylation in malignant gliomas and this has been pinpointed as an epigenetic mechanism reducing MGMT expression levels. The status of MGMT promoter hypermethylation and its relation to tumor progression in gliomas is under extensive study and previous studies have shown conflicting results on the significance of this epigenetic biomarker in relation to the tumor phenotype and clinical outcome. So, in our study, we assessed the role of the epigenetic biomarker; MGMT promoter methylation status, in high-grade glioma patients and correlated the results with the tumor phenotype and clinical outcome. Methods: The study included 40 high-grade glioma patients, assessed for MGMT promoter methylation status using methylation-specific PCR (MSP), and correlated the results with clinico-histopathological parameters and survival using appropriate statistical methodologies. Results: MGMT promoter methylation analysis revealed 65% of patients with the methylated promoter and 35% with unmethylated ones with no significant prognostic or predictive implications related to different treatment modalities (surgical, chemotherapy or radiation), recurrence rate, or overall survival. Conclusion: MGMT promoter methylation status role is not definitive in directing high-grade glioma patients’ clinical decision making. Further studies are needed for investigating its role as an epigenetic marker in high-grade gliomas in Egyptian patients.
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