时间标签：数据日期 2026-10-31 · 生成时间 2026-11-01 05:30（Asia/Shanghai）｜ 检索窗口 PubMed edat 2026/10/28–2026/10/31 ｜ 情报发生日期 2026-10-31
研究问题
However, a substantial subset of GB cases exhibits discordance between MGMT promoter methylation status and MGMT expression levels [].；The aim of this study was therefore to investigate whether DNA methylation patterns in silencer-annotated regions within and surrounding the MGMT locus, including distal regions located up to approximately 1.5 Mb upstream of MGMT, complement existing information on promoter and enhancer methylation.；By integrating data from enhancers and the promoter, we aimed to generate a DNA methylation landscape of MGMT regulatory elements, essential for better understanding the epigenetic mechanisms controlling MGMT expression and their potential clinical implications.
方法
Approval for this study was granted by the Ethics Commission of the Faculty of Medicine at Johannes Kepler University Linz (application number E-39-15).；Cohort tables with relevant clinical parameters and covariates are provided in Supplementary Table and S2.；For Western blot analysis, protein extracts were separated by SDS-PAGE, transferred onto PVDF membranes, and incubated with the monoclonal mouse antibodies anti-human MGMT (clone MT3.1; Merck Millipore, Darmstadt, Germany) and anti-β-Actin (clone AC-15; Sigma-Aldrich, St.；Immunoreactive bands were detected using the ECL Prime Western Blotting Detection Reagent (Cytiva, Marlborough, MA, USA) according to the manufacturer’s instructions and visualized with the ChemiDoc Imaging System (Bio-Rad, Hercules, CA, USA). β-Actin, major component of the cytoskeleton and present at relatively high levels in most eukaryotic cells, served as a lo
核心结论
In this study, we analyzed DNA methylation at 52 CpG sites across eight silencer-annotated regions (“silencers a–h”) located within or near MGMT, including one CpG site directly downstream of silencer g.；Overall, the heatmaps revealed comparable methylation patterns across promoter-associated CpG sites in GB and MBM, with a tendency toward higher methylation levels in GB.；To enable comparison across different genomic contexts, CpGs were divided into the following groups: CpGs located in intergenic silencers; CpGs in the MGMT promoter region commonly used as biomarker in GB (promR); CpGs located upstream or downstream of promR within the promoter; and CpGs located in intronic silencers. ‖ 结论：These results highlight pronounced epigenetic heterogeneity across the MGMT locus and emphasize the importance of CpG-resolved analyses for biomarker development and future functional studies.
局限
A limitation of this study is the incomplete coverage of intergenic silencer-annotated regions in MBM due to limited sample material.；These results highlight pronounced epigenetic heterogeneity across the MGMT locus and emphasize the importance of CpG-resolved analyses for biomarker development and future functional studies.
对本项目的价值
★☆☆☆☆ 相关范围内，作为背景与横向对照收录。
全文来源
PMC JATS 全文（正文 25,495 字符，已过标题/DOI 逐字归属校验）
原文题录
- 英文标题：DNA methylation of silencer-annotated regions at the MGMT locus in the context of promoter and enhancer methylation in glioblastoma and melanoma brain metastases.
- 期刊与标识：Clin Epigenetics · PMID 42958347 · DOI 10.1186/s13148-026-02204-y
A 级证据分级：A 级（同行评议人体研究）
本文属人体研究证据，但需注意：观察性或小样本干预的结论不等于已证实临床获益；效应量与长期安全性仍需更大规模、更长随访的试验验证。
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