MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma
MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma
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DOI：
10.1002/pbc.20803
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发表时间：
2007-04-01
影响因子：
3.2
通讯作者：
Foreman, Nicholas K.
中科院分区：
文献类型：
--
作者：
Donson, Andrew M.;Addo-Yobo, Steven O.;Foreman, Nicholas K.
背景DNA修复基因O-6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）的甲基化导致基因沉默。这种表观遗传修饰与接受替莫唑胺和其他烷化剂的胶质母细胞瘤（GBM）成人患者的良好预后相关。我们探讨了儿童GBM中MGMT启动子甲基化及其与生存率和替莫唑胺敏感性的关系。Procedure.我们对10例儿童GBM的MGMT启动子甲基化进行了回顾性研究。使用2阶段甲基化特异性PCR分析从手术时速冻的肿瘤标本中提取的DNA来确定MGMT的甲基化状态。评估了MGMT启动子甲基化与患者结局和替莫唑胺反应之间的关系。结果我们的10例儿童GBM患者中有4例发现MGMT基因启动子甲基化。MGMT启动子的甲基化与存活率相关（P=0.0005）。MGMT启动子甲基化患者的平均生存时间为13.7个月，而MGMT启动子未甲基化的6例患者的平均生存时间为2.5个月。在接受替莫唑胺治疗的7例患者中，MGMT基因启动子甲基化的患者对治疗的反应更好（P = 0.007）。结论.与成人一样，具有甲基化MGMT启动子的儿童GBM患者受益于替莫唑胺。然而，在该组患者中观察到与总生存期的更强相关性，无论治疗如何。这些数据表明，MGMT甲基化可能是儿童GBM生存的预后因素，也是替莫唑胺敏感性的标志物。儿科血液癌症2007; 48：403-407。(c)2006 Wiley-Liss，Inc.
Background. Methylation of the DNA-repair gene O-6-methylguanine-DNA methyltransferase (MGMT) causes gene silencing. This epigenetic modification has been associated with a favorable prognosis in adult patients with glioblastoma (GBM) who receive temozolomide and other alkylating agents. We explored MGMT promoter methylation in pediatric GBM and its relationship to survival and temozolomide sensitivity. Procedure. We performed a retrospective study of MGMT promoter methylation in 10 pediatric GBM. The methylation status of the MGMT was determined using a 2-stage methylation specific PCR analysis on DNA extracted from turnor specimens which had been snap frozen at surgery. The relationships between MGMT promoter methylation and patient outcome and response to temozolomide were evaluated. Results. Four of our 10 pediatric patients with GBM were found to have methylation of the MGMT gene promoter. Methylation of the MGMT promoter was shown to correlate (P=0.0005) with survival. The average survival time for patients with methylated MGMT was 13.7 months as compared to 2.5 months for the 6 patients with unmethylated MGMT promoter. Of the seven patients that received temozolomide, those patients that had the methylated MGMT gene promoter responded better to treatment (P = 0.007). Conclusions. As in adults, pediatric GBM patients with methylated MGMT promoter benefited from temozolomide. However, a stronger correlation with overall survival, regardless of treatment, was observed in this group of patients. These data suggest that MGMT methylation may be a prognostic factor for survival in pediatric GBM, as well as a marker for temozolomide sensitivity. Pediatr Blood Cancer 2007; 48:403-407. (c) 2006 Wiley-Liss, Inc.