DNA methylation as a universal biomarker

Abstract

Cell-free circulating DNA carries not only tumor-specific changes in its sequence but also distinctive epigenetic marks, namely DNA methylation, in certain GC-rich fragments. These fragments are usually located within the promoters and first exons of many genes, comprising CpG islands. Analysis of DNA methylation using cell-free circulating DNA can facilitate development of very accurate biomarkers for detection, diagnosis, prediction of response to therapy and prognosis of outcomes. Recent data suggest that benign and inflammatory diseases have very specific methylation patterns within cell-free circulating DNA, which are different from the pattern of a malignant tumor of the same organ. In addition, specific methylation patterns have been detected for cancers of different organs, so a differential diagnosis of site-specific cancer appears feasible. Currently, cancer-related applications dominate the field, although methylation-based biomarkers may also be possible for other diseases, including neurodegenerative and psychiatric disorders.

Keywords::

• biomarker
• cancer
• cell-free plasma DNA
• detection
• diagnosis
• methylation
• prediction
• prognosis
• treatment

Acknowledgements

The author is grateful to the members of his laboratory at Rush University Medical Center for their dedication and professionalism. He is also grateful to the reviewers for a thorough review and helpful comments that improved the paper. He is indebted to Alexander Kolchinsky for critical reading of the manuscript. He owes an apology to his colleagues in the field of methylation biomarkers and even wider area of disease biomarkers whose work could not be properly acknowledged due to space limitations.

Financial & competing interests disclosure

This work has been partially supported by R21NS060311, R21RR024420 and DOD W81XWH0710505. Victor Levenson is an employee of the Rush University Medical Center, which has filed for a patent for methylation-based biomarkers in different diseases. The author is also the founder of US Biomarkers, Inc, a start-up biotechnology company, with the mission to develop and implement DNA methylation-based biomarkers. The author has 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.