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脉络丛肿瘤中异常的MGMT(O6-甲基鸟嘌呤-DNA甲基转移酶)启动子甲基化

Aberrant MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation in choroid plexus tumors.

作者信息

Hasselblatt Martin, Mühlisch Jörg, Wrede Brigitte, Kallinger Birgit, Jeibmann Astrid, Peters Ove, Kutluk Tezer, Wolff Johannes E A, Paulus Werner, Frühwald Michael C

机构信息

Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48129, Münster, Germany.

出版信息

J Neurooncol. 2009 Jan;91(2):151-5. doi: 10.1007/s11060-008-9694-2. Epub 2008 Sep 16.

Abstract

Aberrant methylation of the MGMT (O6-methylguanine-DNA methyltransferase) DNA-repair gene is a predictive marker for the response to chemotherapy with alkylating agents (e.g., temozolomide) in malignant gliomas. Since temozolomide is considered for the treatment of choroid plexus tumors, MGMT promoter methylation status was retrospectively assessed in 36 choroid plexus tumors using methylation specific PCR, combined bisulfite restriction analysis (COBRA), and clone sequencing. By methylation specific PCR, all samples demonstrated a signal for MGMT methylation. COBRA confirmed >10% methylation of CpGs 17 and 31 in 58% of tumors. Clone sequencing of six cases methylated by COBRA confirmed aberrant methylation including a previously recognized enhancer element. In conclusion, MGMT promoter methylation is frequent in choroid plexus tumors and can be quantified using COBRA. Determination of MGMT promoter methylation status might be useful for the stratification of patients for alkylator-based treatments in future clinical trials.

摘要

MGMT(O6-甲基鸟嘌呤-DNA甲基转移酶)DNA修复基因的异常甲基化是恶性胶质瘤对烷化剂(如替莫唑胺)化疗反应的预测标志物。由于考虑使用替莫唑胺治疗脉络丛肿瘤,因此采用甲基化特异性PCR、联合亚硫酸氢盐限制分析(COBRA)和克隆测序对36例脉络丛肿瘤的MGMT启动子甲基化状态进行了回顾性评估。通过甲基化特异性PCR,所有样本均显示出MGMT甲基化信号。COBRA证实58%的肿瘤中CpG 17和31的甲基化>10%。对6例经COBRA甲基化的病例进行克隆测序,证实存在异常甲基化,包括一个先前识别的增强子元件。总之,MGMT启动子甲基化在脉络丛肿瘤中很常见,可使用COBRA进行定量。在未来的临床试验中,确定MGMT启动子甲基化状态可能有助于对基于烷化剂治疗的患者进行分层。

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