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.

Can Proopiomelanocortin Methylation Be Used as an Early Predictor of Metabolic Syndrome?

“…However, analysis of methylation using cell-free circulating DNA can facilitate the development of accurate biomarkers for detection and prediction of prognosis and outcomes (34). In another study, a POMC CpG methylation variant was associated with body weight and was detected in DNA from peripheral blood leukocytes (18).…”

DNA Methylation Changes Correlate with Gleason Score and Tumor Stage in Prostate Cancer

“…Neoplasia is not the only contributor to an altered cell-free nucleic acid profile. Other diseases have been shown to affect cell-free plasma DNA levels and composition (Levenson, 2010). This might partly explain the difference between the prevalence of the different epigenetic marks in cell-free plasma DNA, which suggests that markers should be individually investigated.…”

“…The amounts and composition of cell-free plasma DNA can vary over time in individuals suffering from different types of cancer . This is of particular importance in detecting plasma DNA methylation that may be affected by disease status (Levenson, 2010) at different time points. In addition, we used microdissection and cannot rule out the presence of some nontumor DNA in the tumor samples.…”

Septin roles in tumorigenesis

“…Decades ago, it was discovered that a high concentration of cell free circulating DNA (cfcDNA) from solid malignant tumors can be released into the blood and measured (Leon et al, 1977). Comparing the methylation pattern of cfcDNA from the blood of cancer patients to methylation patterns in non-malignant disease has enabled the identification of tumor specific changes and can therefore be used as a biomarker for many cancer types (Levenson, 2010). Colorectal cancer (CRC) is the third leading cause of cancer related deaths in the United States and over the past twenty years the death rate from this disease has been constantly declining.…”