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儿童胶质母细胞瘤中MGMT启动子基因甲基化:采用甲基化特异性多重连接探针扩增技术进行分析

MGMT promoter gene methylation in pediatric glioblastoma: analysis using MS-MLPA.

作者信息

Lee Ji Yeoun, Park Chul-Kee, Park Sung-Hye, Wang Kyu-Chang, Cho Byung-Kyu, Kim Seung-Ki

机构信息

Division of Pediatric Neurosurgery, Department of Neurosurgery, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea.

出版信息

Childs Nerv Syst. 2011 Nov;27(11):1877-83. doi: 10.1007/s00381-011-1525-7. Epub 2011 Jul 26.

Abstract

PURPOSE

Promoter methylation of the O⁶-methylguanine-DNA-methyltransferase (MGMT) gene is widely recognized as an important predictive factor in the treatment of glioblastoma (GBM) patients with temozolomide. However, data regarding the methylation status of the MGMT promoter in pediatric GBM are yet to be elucidated.

METHODS

Nineteen tissue samples of pediatric GBM were evaluated for the MGMT promoter methylation status using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). Methylation status was also evaluated using methylation-specific polymerase chain reaction (MSP) for 17 of the 19 patients. The correlation between MGMT promoter methylation and clinical outcome was assessed.

RESULTS

Three of the 19 patients (16%) showed methylation of the MGMT promoter, according to MS-MLPA, as did 1 of the 17 (6%), according to MSP. The methylation status did not seem to have a definite effect on clinical outcome.

CONCLUSIONS

Pediatric GBMs rarely have methylated MGMT promoters. With a better clinical outcome and lower methylation rate than their adult counterparts, it may be suggested that, for pediatric GBM, MGMT promoter methylation does not play a significant role as a prognostic factor.

摘要

目的

O⁶-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子甲基化被广泛认为是胶质母细胞瘤(GBM)患者替莫唑胺治疗中的一个重要预测因素。然而,小儿GBM中MGMT启动子的甲基化状态的数据尚未阐明。

方法

使用甲基化特异性多重连接依赖探针扩增(MS-MLPA)对19例小儿GBM组织样本的MGMT启动子甲基化状态进行评估。对19例患者中的17例还使用甲基化特异性聚合酶链反应(MSP)评估甲基化状态。评估MGMT启动子甲基化与临床结果之间的相关性。

结果

根据MS-MLPA,19例患者中有3例(16%)显示MGMT启动子甲基化,根据MSP,17例中有1例(6%)显示甲基化。甲基化状态似乎对临床结果没有明确影响。

结论

小儿GBM很少有MGMT启动子甲基化。与成人GBM相比,小儿GBM具有更好的临床结果和更低的甲基化率,这可能表明,对于小儿GBM,MGMT启动子甲基化作为预后因素并不起重要作用。

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