Epigenetic Study of Plasma Circulating DNA in Prostate Cancer

Malignant cells exhibit epigenetic differences compared to normal cells, which can also be detected in the cell-free circulating DNA (cirDNA) of bodily fluids. DNA modification studies in cirDNA may lead to the development of non-invasive cancer biomarkers. This thesis investigates plasma cirDNA modifications of prostate cancer patients, benign prostate hyperplasia patients, and men without any known prostate disease. A modification-sensitive restriction enzyme approach was used to enrich the modified DNA fractions, which were interrogated on CpG island- and Affymetrix tiling microarrays. Our initial discovery screen identified a number of differentially modified genes and non-coding loci between PCa patients and controls; a subset of candidate loci were verified using bisulfite pyrosequencing. We applied machine-learning techniques to develop a multi-locus biomarker set, which exhibited promising predictive performance in distinguishing cancer patients from unaffected controls. Our results suggest that epigenomics of cirDNA is a promising source for diagnostic non-invasive biomarkers of solid tumors.M.Sc.2017-12-01 00:00:0