DNA Methylation Biomarkers in Cancer: Current Clinical Utility and Future Perspectives

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Epigenetic alterations are related to inherited but reversible changes in modifications that regulate gene activity beyond the DNA sequence. DNA methylation is the best characterized epigenetic modification, controlling DNA stability, DNA structure, transcription, and regulation, contributing to normal development and differentiation. In this section, we first discuss the cellular functions of DNA methylation and focus on how this fundamental biological process is impaired in cancer. Changes in DNA methylation status in cancer have been heralded as promising targets for the development of diagnostic, prognostic, and predictive biomarkers due to their noninvasive accessibility in bodily fluids (such as blood, urine, stool), reversibility, stability, and frequency. The absence of markers for definitive diagnosis of most types of cancer and, in some cases, DNA methylation biomarkers being more specific and sensitive than commonly used protein biomarkers indicate a strong need for continued research to expand DNA methylation markers. Although the information on changes in DNA methylation status in cancer and research on its clinical relevance is rapidly increasing, the number of DNA methylation biomarkers currently available as commercial tests is very small. Here, we focus on the importance of DNA methylation location and target genes likely to be developed in the future for the development of biomarkers in addition to existing commercial tests. Following a detailed study of possible target genes, we summarize the current clinical application status of the most studied and validated DNA methylation biomarkers, including SEPT9, SDC2, BMP3, NDRG4, SFRP2, TFPI2, VIM and MGMT.