Recent advances in understanding DNA methylation of prostate cancer

Abstract

Epigenetic modifications, such as DNA methylation, is widely studied in cancer. DNA methylation patterns have been shown to distinguish between benign and malignant tumors in various cancers, including prostate cancer. It may also contribute to oncogenesis, as it is frequently associated with downregulation of tumor suppressor genes. Aberrant patterns of DNA methylation, in particular the CpG island hypermethylator phenotype (CIMP), have shown associative evidence with distinct clinical features and outcomes, such as aggressive subtypes, higher Gleason score, prostate-specific antigen (PSA), and overall tumor stage, overall worse prognosis, as well as reduced survival. In prostate cancer, hypermethylation of specific genes is significantly different between tumor and normal tissues. Methylation patterns could distinguish between aggressive subtypes of prostate cancer, including neuroendocrine prostate cancer (NEPC) and castration resistant prostate adenocarcinoma. Further, DNA methylation is detectable in cell-free DNA (cfDNA) and is reflective of clinical outcome, making it a potential biomarker for prostate cancer. This review summarizes recent advances in understanding DNA methylation alterations in cancers with the focus on prostate cancer. We discuss the advanced methodology used for evaluating DNA methylation changes and the molecular regulators behind these changes. We also explore the clinical potential of DNA methylation as prostate cancer biomarkers and its potential for developing targeted treatment of CIMP subtype of prostate cancer.

Keywords: 5mC; CIMP; DNA methylation; epigenetic regulation; mCRPC.