Epigenetics and CTCs: New biomarkers and impact on tumor biology

DNA methylation is one of the best-known epigenetic markers and plays a critical role in the control of gene activity and the architecture of the nucleus of the cell. Epigenetic alterations and especially DNA methylation have a high potential to provide valuable and innovative cancer biomarkers. Liquid biopsy is a unique minimally invasive tool for the management of cancer patients based on the extraction of information through detailed molecular analysis of circulating genetic material in peripheral blood and allows us to characterize the evolution of a solid tumor in real time. DNA methylation in combination with liquid biopsy is very powerful when it comes to providing circulating epigenetic biomarkers of clinical importance. Numerous DNA methylation markers are now being tested in liquid biopsies as potential biomarkers in various types of cancer. DNA methylation is mostly being studied in ctDNA but there are also a small number of studies up to now performed in gDNA isolated from CTCs. A highly important dimension of the combination of liquid biopsy/DNA methylation analysis is its high potential for early cancer detection since alterations in DNA methylation in plasma can be detected very early during cancer pathogenesis. Methylated DNA, modified nucleosomes and noncoding RNAs can be used as blood circulating epigenetic biomarkers for real-time and minimally-invasive cancer monitoring. DNA methylation is very promising and powerful in providing novel biomarkers for improving cancer diagnostics, while another important dimension in this field is the use of DNA methylation inhibitors in cancer treatment. In this chapter we present the current findings on epigenetic alterations detected in CTCs in various types of cancer, and further discuss their potential as novel liquid biopsy-based DNA methylation biomarkers.