The methylome and cell-free DNA: current applications in medicine and pediatric disease

ABSTRACT: DNA methylation is an epigenetic mechanism that contributes to cell regulation and development, and different methylation patterns allow for the identification of cell and tissue type. Cell-free DNA (cfDNA) is composed of small circulating fragments of DNA found in plasma and urine. Total cfDNA levels correlate with the presence of inflammation and tissue injury in a variety of disease states. Unfortunately, the utility of cfDNA is limited by its lack of tissue or cell-type specificity. However, methylome analysis of cfDNA allows the identification of the tissue or cell type from which cfDNA originated. Thus, methylation patterns in cfDNA from tissues isolated from direct study may provide windows into health and disease states, thereby serving as a “liquid biopsy”. This review will discuss methylation and its role in establishing cellular identity, cfDNA as a biomarker and its pathophysiologic role in the inflammatory process, and the ways cfDNA and methylomics can be jointly applied in medicine. IMPACT: Cell-free DNA (cfDNA) is increasingly being used as a noninvasive diagnostic and disease-monitoring tool in pediatric medicine. However, the lack of specificity of cfDNA limits its utility. Identification of cell type-specific methylation signatures can help overcome the limited specificity of cfDNA. As knowledge of the cfDNA methylome improves, cfDNA will be more broadly applied in medicine, such that clinicians will need to understand the methods and applications of its use.