Methylome-wide Sequencing Detects DNA Hypermethylation Distinguishing Indolent from Aggressive Prostate Cancer.
Methylome-wide Sequencing Detects DNA Hypermethylation Distinguishing Indolent from Aggressive Prostate Cancer.
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DOI：
10.1016/j.celrep.2015.10.078
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发表时间：
2015-12-15
期刊：
影响因子：
8.8
通讯作者：
Ting AH
中科院分区：
文献类型：
--
作者：
Bhasin JM;Lee BH;Matkin L;Taylor MG;Hu B;Xu Y;Magi-Galluzzi C;Klein EA;Ting AH
了解前列腺癌生物学的一个关键需要是表征惰性和侵袭性病例之间的分子差异。由于DNA甲基化可以捕获肿瘤的调节状态，我们分析了良性前列腺组织、低级别和高级别前列腺癌之间全基因组的差异甲基化模式，发现了高级别疾病特有的广泛的局灶性高甲基化区域。这些高甲基化区域不仅发生在基因的启动子中，也发生在基因体中，以及富含DNA-蛋白质结合位点的基因间区域。与现有RNA-seq和生存数据的整合揭示了DNA甲基化与基因表达降低相关的区域，这些基因表达降低与不良结局相关。侵袭性疾病的特异性区域与惰性和侵袭性疾病共有的区域具有不同功能的基因邻近。我们的甲基化变化纲要揭示了惰性和侵袭性前列腺癌之间的关键分子差异。
A critical need in understanding the biology of prostate cancer is characterizing the molecular differences between indolent and aggressive cases. Because DNA methylation can capture the regulatory state of tumors, we analyzed differential methylation patterns genome-wide among benign prostatic tissue, low grade, and high grade prostate cancer and found extensive, focal hypermethylation regions unique to high grade disease. These hypermethylation regions occurred not only in the promoters of genes, but also in gene bodies, and at intergenic regions that are enriched for DNA-protein binding sites. Integration with existing RNA-seq and survival data revealed regions where DNA methylation correlates with reduced gene expression associated with poor outcome. Regions specific to aggressive disease are proximal to genes with distinct functions from regions shared by indolent and aggressive disease. Our compendium of methylation changes reveals crucial molecular distinctions between indolent and aggressive prostate cancer.