The importance of DNA methylation in prostate cancer development

• Published in: The Journal of steroid biochemistry and molecular biology 2017-02, Vol.166, p.1-15
• Main Authors: Massie, Charles E., Mills, Ian G., Lynch, Andy G.
• Format: Article
• Language: English
• Subjects: Androgen receptors; Biomarkers; Biomarkers, Tumor - metabolism; CpG Islands; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenesis, Genetic; Epigenetic; Gene Expression Regulation, Neoplastic; Genome, Human; Humans; Male; Metabolism; Methylation; Mitochondria; Mitochondria - metabolism; Promoter Regions, Genetic; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Receptors, Androgen - genetics; Tumor cell lines
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2016.04.009

•Many DNA methylation changes are observed between benign and cancerous prostate tissue.•DNA methylation changes are frequently early and recurrent, suggesting a functional role.•Androgen-driven metabolic processes in the prostate impinge on DNA methylation.•Prostate cancer cell lines offer a good model for some methylation changes, but not all.•Clinical/genomic associations have been reported, but multi-region sampling studies are needed. After briefly reviewing the nature of DNA methylation, its general role in cancer and the tools available to interrogate it, we consider the literature surrounding DNA methylation as relating to prostate cancer. Specific consideration is given to recurrent alterations. A list of frequently reported genes is synthesized from 17 studies that have reported on methylation changes in malignant prostate tissue, and we chart the timing of those changes in the diseases history through amalgamation of several previously published data sets. We also review associations with genetic alterations and hormone signalling, before the practicalities of investigating prostate cancer methylation using cell lines are assessed. We conclude by outlining the interplay between DNA methylation and prostate cancer metabolism and their regulation by androgen receptor, with a specific discussion of the mitochondria and their associations with DNA methylation.