The Genomic Impact of DNA CpG Methylation on Gene Expression; Relationships in Prostate Cancer.
The Genomic Impact of DNA CpG Methylation on Gene Expression; Relationships in Prostate Cancer.
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DOI：
10.3390/biom7010015
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发表时间：
2017-02-14
期刊：
影响因子：
5.5
通讯作者：
Campbell MJ
中科院分区：
文献类型：
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作者：
Long MD;Smiraglia DJ;Campbell MJ
DNA CpG 甲基化过程已被广泛研究了 50 多年，并揭示了 CpG 岛甲基化状态变化与基因表达之间的关联。因此，DNA CpG 甲基化参与发育和稳态过程中基因表达的控制，并且是一种癌症驱动机制。全基因组技术和复杂统计分析方法的发展开创了一个广泛分析 DNA CpG 甲基化、基因表达和肿瘤状态之间关系的时代，例如在癌症领域。例如，通过癌症基因组图谱 (TCGA) 的研究人员，此类基因组数据量显着增加，使得能够剖析 DNA CpG 甲基化密度和分布、基因表达和肿瘤结果之间的关系。通过这种方式，现在可以测试 DNA CpG 甲基化和基因表达变化之间的全基因组相关性是可测量的。也许令人惊讶的是，这些关联只能在数百个而不是数千个基因中检测到，而且相关的方向既有正的也有负的。这或许表明癌症系统中的 CpG 甲基化事件可以作为疾病驱动因素，但其影响可能比想象的更为有限。此外，正相关和负相关表明直接和间接事件以及不完整的理解。在前列腺癌 TCGA 队列中，我们检查了控制 DNA 甲基化的基因表达、已知的 DNA 甲基化靶标与肿瘤状态之间的关系。这表明，控制 S-腺苷-L-甲硫氨酸 (SAM) 合成的基因与侵袭性肿瘤子集中 DNA 甲基化靶标的表达改变相关。
The process of DNA CpG methylation has been extensively investigated for over 50 years and revealed associations between changing methylation status of CpG islands and gene expression. As a result, DNA CpG methylation is implicated in the control of gene expression in developmental and homeostasis processes, as well as being a cancer-driver mechanism. The development of genome-wide technologies and sophisticated statistical analytical approaches has ushered in an era of widespread analyses, for example in the cancer arena, of the relationships between altered DNA CpG methylation, gene expression, and tumor status. The remarkable increase in the volume of such genomic data, for example, through investigators from the Cancer Genome Atlas (TCGA), has allowed dissection of the relationships between DNA CpG methylation density and distribution, gene expression, and tumor outcome. In this manner, it is now possible to test that the genome-wide correlations are measurable between changes in DNA CpG methylation and gene expression. Perhaps surprisingly is that these associations can only be detected for hundreds, but not thousands, of genes, and the direction of the correlations are both positive and negative. This, perhaps, suggests that CpG methylation events in cancer systems can act as disease drivers but the effects are possibly more restricted than suspected. Additionally, the positive and negative correlations suggest direct and indirect events and an incomplete understanding. Within the prostate cancer TCGA cohort, we examined the relationships between expression of genes that control DNA methylation, known targets of DNA methylation and tumor status. This revealed that genes that control the synthesis of S-adenosyl-l-methionine (SAM) associate with altered expression of DNA methylation targets in a subset of aggressive tumors.