Genome-wide Distribution and Regulation of DNA Methylation and Hydroxymethylation in Prostate Cancer

Prostate cancer (PCa) is the most common malignancy in men. Epigenetic alterations, including DNA methylation, significantly influence disease pathogenesis. Aberrant methylation of the cytosine base (5mC) transcriptionally regulates several genes associated with PCa development. Recent discovery that 5mC marks are converted to DNA hydroxymethylation (5hmC) marks by ten-eleven translocation (TET) proteins has opened avenues for epigenome regulation. The intent of my MSc research was to define the genome-wide DNA methylation and hydroxymethylation patterns in prostate cell lines, benign and cancerous, using next-generation sequencing technology and bioinformatics analysis. I defined regions of differential methylation between normal and cancer, and suggest novel biomarkers for the disease. Additionally, this is the first study to discover the landscape of DNA hydroxymethylation in PCa, which suggests enrichment in specific genomic regions. Furthermore, I revealed pathways potentially regulated by 5mC and 5hmC marks to expand our knowledge of aberrant epigenetic processes in PCa pathogenesis.M.Sc.2016-11-11 00:00:0