Aberrant DNA methylation is frequently detected in gastrointestinal tumors, and can therefore potentially be used to screen, diagnose, prognosticate, and predict colorectal cancers (CRCs). Although colonoscopic screening remains the gold standard for CRC screening, this procedure is invasive, expensive, and suffers from poor patient compliance. Methylated DNA is an attractive choice for a biomarker substrate because CRCs harbor hundreds of aberrantly methylated genes. Furthermore, abundance in extracellular environments and resistance to degradation and enrichment in serum, stool, and other noninvasive bodily fluids, allows quantitative measurements of methylated DNA biomarkers. This article describes the most important studies that investigated the efficacy of serum- or stool-derived methylated DNA as population-based screening biomarkers in CRC, details several mechanisms and factors that control DNA methylation, describes a better use of prevailing technologies that discover novel DNA methylation biomarkers, and illustrates the diversity of demethylating agents and their applicability toward clinical impact.
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