Challenges for the application of DNA methylation biomarkers in molecular diagnostic testing for cancer

Abstract

Aberrant DNA methylation is ubiquitous in human cancer and has been shown to occur early during carcinogenesis, thus providing attractive potential biomarkers for the early detection of cancer. The introduction of genome-wide DNA methylation analysis comparing tumor and nonmalignant tissues resulted in the discovery of many regions that undergo aberrant methylation during carcinogenesis. Those regions can potentially be used as biomarkers for cancer detection. However, a biomarker will be useful for screening or early detection of cancer only if it can be detected in a noninvasive or minimally invasive fashion without tissue biopsy. The authors discuss the challenges in translating DNA methylation biomarkers to cancer diagnosis – including obstacles in assay development, tissue-specific methylation load on tumor suppressor genes, detecting markers with sufficient sensitivity and specificity in the periphery, and ways in which these obstacles can be overcome.

Keywords::

• biomarkers
• cancer detection
• DNA methylation
• molecular diagnostic testing

Financial & competing interests disclosure

This work was supported by NIH grant R01CA125642 (Y-H Su) and Prevent Cancer Foundation Postdoctoral Fellowship Award (S Jain). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.