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Biomolecules 2017, 7(1), 15; doi:10.3390/biom7010015

The Genomic Impact of DNA CpG Methylation on Gene Expression; Relationships in Prostate Cancer

1
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA
2
College of Pharmacy, Pharmaceutics and Pharmaceutical Chemistry, 536 Parks Hall, 500 West 12th Ave., The Ohio State University, Columbus, OH 43210, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Gerda Egger and Melanie R. Hassler
Received: 30 November 2016 / Revised: 23 January 2017 / Accepted: 6 February 2017 / Published: 14 February 2017
(This article belongs to the Special Issue DNA Methylation and Cancer)
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Abstract

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. View Full-Text
Keywords: CpG methylation; gene expression; genome-wide; prostate cancer; Indolethylamine N-Methyltransferase; Methionine Adenosyltransferase 2B CpG methylation; gene expression; genome-wide; prostate cancer; Indolethylamine N-Methyltransferase; Methionine Adenosyltransferase 2B
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Long, M.D.; Smiraglia, D.J.; Campbell, M.J. The Genomic Impact of DNA CpG Methylation on Gene Expression; Relationships in Prostate Cancer. Biomolecules 2017, 7, 15.

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