DNA Methylation Changes in Prostate Cancer: Current Developments and Future Clinical Implementation

Mohammad Obaidul Hoque

Disclosures

Expert Rev Mol Diagn. 2009;9(3):243-257. 

In This Article

Abstract and Introduction

Abstract

Promoter hypermethylation is associated with the loss of expression of tumor-suppressor genes in cancer. Currently, several genome-wide technologies are available and have been utilized to examine the extent of DNA methylation in discovery-based studies involving several physiological and disease states. Although early in the process, aberrant DNA methylation is gaining strength in the fields of cancer risk assessment, diagnosis and therapy monitoring in different cancer types. There is a need to improve existing methods for early diagnosis of prostate cancer and to identify men at risk for developing aggressive disease. Because of the ubiquity of DNA methylation changes and the ability to detect methylated DNA in several body fluids (e.g., blood and urine), this specifically altered DNA may serve, on one hand, as a possible new screening marker for prostate cancer and, on the other hand, as a tool for therapy monitoring in patients having had neoplastic disease of the prostate. Since many prostate cancer patients present with advanced disease and some present with nonspecific elevation of prostate-specific antigen without prostate cancer, early detection with high specificity and sensitivity is considered to be one of the most important approaches to reduce mortality and unwanted tension of the men with high prostate-specific antigen. Therefore, an effective screening test would have substantial clinical benefits. Furthermore, methylation markers of risk of progression of disease in patients having prostate cancer permits immediate commencement of specific treatment regimens and probably longer survival and better quality of life. This review illustrates the current benefits and limitations of potentially useful prostate cancer methylation markers that have considerable existing data and touches upon other future markers as well as the field of methylation in prostate cancer.

Introduction

The successful completion of the Human Genome Project has resulted in the annotation of approximately 30,000 genes. The major key question facing the scientific and clinical communities has been how to use this information for the benefit of cancer patients, for example through early detection, prognosis, therapeutic response and monitoring of disease. Hypermethylation or hypomethylation of the promoter region (one of the epigenetic alterations) inactivates or activates certain genes that are related to cancer. Different approaches to the study of promoter region methylation have been developed in recent years. Information from the Human Genome Project facilitates these approaches. This review describes the different ways that methylation of the promoter region of different key cancer genes has led to the identification of novel biomarkers that have affected, or that have the potential to affect, the clinical management of human prostate cancer. A survey of biomarkers identified by other approaches is provided elsewhere.[1]

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