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胶质母细胞瘤长期幸存者中频繁的 MGMT(O(6)-甲基鸟嘌呤-DNA 甲基转移酶)甲基化:单机构经验。

Frequent MGMT (0(6)-methylguanine-DNA methyltransferase) hypermethylation in long-term survivors of glioblastoma: a single institution experience.

机构信息

Applied Cancer Research-Institution for Translational Research Vienna (ACR-ITR VIEnna/CEADDP), Vienna, Austria.

出版信息

Radiol Oncol. 2010 Jun;44(2):113-20. doi: 10.2478/v10019-010-0023-y. Epub 2010 May 24.

DOI:10.2478/v10019-010-0023-y
PMID:22933901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3423688/
Abstract

BACKGROUND

The aim of this retrospective study was to analyse the MGMT (0(6)-methylguanine-DNA methyltransferase) promoter methylation status in long-term surviving (≥ 3 years) patients with glioblastoma multiforme (GBM).

METHODS

The methylation status of the MGMT promoter was determined by bisulfite modification of the DNA and subsequent methylation-specific polymerase-chain-reaction (MSP). DNA was extracted from routinely formalin-fixed and paraffin-embedded tumour tissue samples.

RESULTS

MSP yielded interpretable results in only 14 of 33 (42%) long-term surviving patients with GBM. A methylated band was seen in 3 of 14, methylated as well as unmethylated bands in 8 of 14 and an only unmethylated band in 3 of 14 patients, thus, yielding MGMT promoter methylation in 11 of 14 patients. The two groups of patients with methylated and unmethylated MGMT promoter status were too small to draw any firm statistical conclusions.

CONCLUSIONS

Long-term surviving patients with GBM have very frequently intratumoural MGMT promoter methylation. This phenomenon discriminates long-term survivors from a non-selected group of patients with GBM. The standardization of the MSP for the determination of the MGMT promoter methylation status seems to be necessary in order to make this methodology a more reliable one.

摘要

背景

本回顾性研究旨在分析胶质母细胞瘤(GBM)中长时间存活(≥3 年)患者的 MGMT(0(6)-甲基鸟嘌呤-DNA 甲基转移酶)启动子甲基化状态。

方法

通过 DNA 的亚硫酸氢盐修饰和随后的甲基化特异性聚合酶链反应(MSP)来确定 MGMT 启动子的甲基化状态。从常规福尔马林固定和石蜡包埋的肿瘤组织样本中提取 DNA。

结果

仅在 33 名长期存活的 GBM 患者中的 14 名中获得了可解释的 MSP 结果。在 14 名患者中,3 名患者出现甲基化带,8 名患者出现甲基化和非甲基化带,3 名患者仅出现非甲基化带,因此,14 名患者中有 11 名患者存在 MGMT 启动子甲基化。MGMT 启动子甲基化和非甲基化的两组患者样本量太小,无法得出任何确凿的统计结论。

结论

GBM 中长时间存活的患者肿瘤内 MGMT 启动子甲基化非常频繁。这种现象将长期存活者与未选择的 GBM 患者区分开来。为了使该方法更可靠,有必要对 MSP 进行标准化,以确定 MGMT 启动子的甲基化状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/3423688/99e30e40ed4e/rado-44-02-113f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/3423688/433a6d9a4aa2/rado-44-02-113f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/3423688/99e30e40ed4e/rado-44-02-113f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/3423688/433a6d9a4aa2/rado-44-02-113f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fc6f/3423688/99e30e40ed4e/rado-44-02-113f2.jpg

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