WOMEN IN CANCER THEMATIC REVIEW: Diverse functions of DNA methylation: implications for prostate cancer and beyond.
WOMEN IN CANCER THEMATIC REVIEW: Diverse functions of DNA methylation: implications for prostate cancer and beyond.
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DOI：
10.1530/erc-16-0306
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发表时间：
2016-11
影响因子：
3.9
通讯作者：
Thomas J. Sweet;A. Ting
中科院分区：
文献类型：
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作者：
Thomas J. Sweet;A. Ting
前列腺癌是世界范围内男性最常见的恶性肿瘤之一。目前的临床筛查确保大多数前列腺癌在器官局限性时被诊断出来，但疾病结局差异很大。因此，正在寻求更好地了解有助于前列腺癌侵袭性的分子特征。对于许多癌症，CpG二核苷酸中胞嘧啶DNA甲基化的异常全基因组模式将肿瘤与正常组织区分开来，并通过改变转录组而促进疾病进展。在前列腺癌中，最近的基因组研究确定了癌症和基因启动子、基因体、基因3'末端和远端调控元件中的高等级特异性差异DNA甲基化。使用从发展和疾病系统的例子，我们将讨论如何在这些基因组环境中的DNA甲基化可以通过调节转录起始，选择性转录起始位点选择，选择性前mRNA剪接和选择性多聚腺苷酸化的转录组多样性。来自相同基因的替代转录物通常表现出改变的蛋白质编码潜力、可翻译性、稳定性和/或定位。所有这些都可以在细胞中产生功能性后果。在未来的工作中，重要的是确定前列腺癌中的DNA甲基化异常是否通过这些机制中的一些或全部来改变转录组，以及这些DNA甲基化介导的转录组改变是否影响前列腺肿瘤发生和侵袭性。
Prostate cancer is one of the most common malignancies in men worldwide. Current clinical screening ensures that most prostate cancers are diagnosed while still organ confined, but disease outcome is highly variable. Thus, a better understanding of the molecular features contributing to prostate cancer aggressiveness is being sought. For many cancers, aberrant genome-wide patterns of cytosine DNA methylation in CpG dinucleotides distinguish tumor from normal tissue and contribute to disease progression by altering the transcriptome. In prostate cancer, recent genomic studies identified cancer and high grade-specific differential DNA methylation in gene promoters, gene bodies, gene 3' ends and at distal regulatory elements. Using examples from developmental and disease systems, we will discuss how DNA methylation in each of these genomic contexts can contribute to transcriptome diversity by modulating transcription initiation, alternative transcription start site selection, alternative pre-mRNA splicing and alternative polyadenylation. Alternative transcripts from the same gene often exhibit altered protein-coding potential, translatability, stability and/or localization. All of these can have functional consequences in cells. In future work, it will be important to determine if DNA methylation abnormalities in prostate cancer modify the transcriptome through some or all of these mechanisms and if these DNA methylation-mediated transcriptome alterations impact prostate tumorigenesis and aggressiveness.