非小细胞肺癌中 DNA 修复基因启动子甲基化的重新评估
A critical re-assessment of DNA repair gene promoter methylation in non-small cell lung carcinoma.
机构信息
1] Molecular Pathology Research and Development Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, 8006, Australia [2] Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Medical Research, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia [3] Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia.
1] Translational Genomics and Epigenomics Laboratory, Ludwig Institute for Medical Research, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Heidelberg, Victoria, 3084, Australia [2] Department of Pathology, University of Melbourne, Parkville, Victoria, 3010, Australia.
出版信息
Sci Rep. 2014 Feb 26;4:4186. doi: 10.1038/srep04186.
DNA repair genes that have been inactivated by promoter methylation offer potential therapeutic targets either by targeting the specific repair deficiency, or by synthetic lethal approaches. This study evaluated promoter methylation status for eight selected DNA repair genes (ATM, BRCA1, ERCC1, MGMT, MLH1, NEIL1, RAD23B and XPC) in 56 non-small cell lung cancer (NSCLC) tumours and 11 lung cell lines using the methylation-sensitive high resolution melting (MS-HRM) methodology. Frequent methylation in NEIL1 (42%) and infrequent methylation in ERCC1 (2%) and RAD23B (2%) are reported for the first time in NSCLC. MGMT methylation was detected in 13% of the NSCLCs. Contrary to previous studies, methylation was not detected in ATM, BRCA1, MLH1 and XPC. Data from The Cancer Genome Atlas (TCGA) was consistent with these findings. The study emphasises the importance of using appropriate methodology for accurate assessment of promoter methylation.
通过启动子甲基化失活的 DNA 修复基因提供了潜在的治疗靶点，既可以针对特定的修复缺陷，也可以通过合成致死的方法。本研究使用甲基化敏感高分辨率熔解（MS-HRM）方法，评估了 56 例非小细胞肺癌（NSCLC）肿瘤和 11 个肺细胞系中 8 个选定的 DNA 修复基因（ATM、BRCA1、ERCC1、MGMT、MLH1、NEIL1、RAD23B 和 XPC）的启动子甲基化状态。首次在 NSCLC 中报道了 NEIL1（42%）频繁甲基化和 ERCC1（2%）和 RAD23B（2%）罕见甲基化。MGMT 甲基化在 13%的 NSCLC 中被检测到。与之前的研究不同，ATM、BRCA1、MLH1 和 XPC 中未检测到甲基化。来自癌症基因组图谱（TCGA）的数据与这些发现一致。该研究强调了使用适当的方法来准确评估启动子甲基化的重要性。
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