Promoter hypermethylation in prostate cancer

Abstract

Background: The prostate gland is the most common site of cancer and the second leading cause of cancer mortality in American men. It is well known that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer.

Methods: This review discusses current information on methylated genes associated with prostate cancer development and progression.

Results: Over 30 genes have been investigated for promoter methylation in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is reviewed.

Conclusions: These findings may provide new information of the pathogenesis of prostate cancer. Certain epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use.

Figure

Role of DNA methylation in expression. Unmethylated and methylated CpG sites are indicated by yellow and black circles, respectively. Gene 1 and gene 2 are rarely methylated and therefore expressed. Densely hypermethylated CpG islands in the promoter region of a tumor suppressor gene (TSG) in tumor inhibit expression. Hypomethylation in the promoter region of oncogene in tumor reactivates a transcription process.