DNA methylation in cancer development and progression

Genetic biomarkers for cancer found in the circulation typically involve measurement of mutations in genomic DNA. However, more recently a number of specific epigenetic changes in cancer such as DNA methylation at several sites on important cancer genes (e.g., oncogenes and tumor suppresser genes) have been identified in a number of important tumors such as breast, lung, ovarian, liver and colon, among others. These epigenetic changes are believed to be directly involved in the development and progression of cancer. Thus, the detection and quantification of DNA methylation of specific cancer genes in the circulation has led to the development of a new biomarker and a new approach for the evaluation of cancer. Measurement of DNA methylation in the circulation should be much less invasive and perhaps more accurate than traditional methods such as radiation imaging and tumor biopsy. Furthermore, other noninvasive and nonradiation methods such as magnetic resonance imaging and tissue ultrasound appear to be much less effective for the detection and/or quantification of early or minimal tumor development. Accordingly, there is considerable interest in the identification of specific sites of genetic methylation in tumor cells and the detection and quantification of the extremely small quantities of this epigenetic biomarker in the circulation. This article will review the involvement of DNA methylation in the development and progression of cancer. In addition, a review of current and future quantification methodology and the development of panels of DNA methylation biomarkers and combinations of biomarkers will be examined. These new DNA methylation biomarkers should present an important improvement in the early detection, selection of the most effective treatment options and assessment of tumor responsiveness to appropriate therapy.