title: The Genomic Impact of DNA CpG Methylation on Gene Expression; Relationships in Prostate Cancer.
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 ofS-adenosyl-l-methionine (SAM) associate with altered expression of DNA methylation targets in a subset of aggressive tumors.
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Mark.long@roswellpark.org.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Long
authors.affiliation: Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. dominic.smiraglia@roswellpark.org.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Smiraglia
authors.affiliation: College of Pharmacy, Pharmaceutics and Pharmaceutical Chemistry, 536 Parks Hall, 500 West 12th Ave., The Ohio State University, Columbus, OH 43210, USA. Campbell.1933@osu.org.
authors.forename: Moray J
authors.initials: MJ
authors.lastname: Campbell
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D030541:Databases, Genetic; D057890:Epigenomics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D012436:S-Adenosylmethionine
keywords: CpG methylation; Indolethylamine N-Methyltransferase; Methionine Adenosyltransferase 2B; gene expression; genome-wide; prostate cancer