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首页> 美国卫生研究院文献>Genes >Heterogeneous DNA Methylation Patterns in the GSTP1 Promoter Lead to Discordant Results between Assay Technologies and Impede Its Implementation as Epigenetic Biomarkers in Breast Cancer
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Heterogeneous DNA Methylation Patterns in the GSTP1 Promoter Lead to Discordant Results between Assay Technologies and Impede Its Implementation as Epigenetic Biomarkers in Breast Cancer

机译：GSTP1启动子中的异质DNA甲基化模式导致检测技术之间的结果不一致并阻碍了其作为乳腺癌的表观遗传标记的实现

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摘要

Altered DNA methylation patterns are found in many diseases, particularly in cancer, where the analysis of DNA methylation holds the promise to provide diagnostic, prognostic and predictive information of great clinical value. Methylation of the promoter-associated CpG island of GSTP1 occurs in many hormone-sensitive cancers, has been shown to be a biomarker for the early detection of cancerous lesions and has been associated with important clinical parameters, such as survival and response to treatment. In the current manuscript, we assessed the performance of several widely-used sodium bisulfite conversion-dependent methods (methylation-specific PCR, MethyLight, pyrosequencing and MALDI mass-spectrometry) for the analysis of DNA methylation patterns in the GSTP1 promoter. We observed large discordances between the results obtained by the different technologies. Cloning and sequencing of the investigated region resolved single-molecule DNA methylation patterns and identified heterogeneous DNA methylation patterns as the underlying cause of the differences. Heterogeneous DNA methylation patterns in the GSTP1 promoter constitute a major obstacle to the implementation of DNA methylation-based analysis of GSTP1 and might explain some of the contradictory findings in the analysis of the significance of GSTP1 promoter methylation in breast cancer.
机译：在许多疾病中，尤其是在癌症中发现了改变的DNA甲基化模式，其中对DNA甲基化的分析有望提供具有重大临床价值的诊断，预后和预测信息。 GSTP1的与启动子相关的CpG岛的甲基化发生在许多激素敏感性癌症中，已被证明是早期发现癌性病变的生物标志物，并与重要的临床参数（例如存活率和对治疗的反应）相关。在当前的手稿中，我们评估了几种广泛使用的亚硫酸氢钠转化依赖性方法（甲基化特异性PCR，MethyLight，焦磷酸测序和MALDI质谱分析）的性能，用于分析GSTP1启动子中的DNA甲基化模式。我们观察到了不同技术所获得的结果之间的巨大差异。所研究区域的克隆和测序解决了单分子DNA甲基化模式，并将异质DNA甲基化模式确定为差异的根本原因。 GSTP1启动子中的异质DNA甲基化模式构成了基于DNA甲基化的GSTP1分析实施的主要障碍，并可能解释了GSTP1启动子甲基化在乳腺癌中的意义分析中的一些矛盾发现。

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