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Epigenetic Biomarkers

Recent reports indicates that CtDNA and exosome levels are higher in cancer patients, however the physi­ological events that lead to the increase of CtDNA/exosomes levels during cancer development and progression are still not well understood. Analyses of CtDNA and tumor exosome contents will allow the detection of tumor-related epi­genetic and genetic alterations that are relevant to cancer develop­ment and progression. Epigenetic modifications such as DNA methylation and histone acetylation are important mechanisms of gene (e.g. tumor suppressor and oncogenes) regulation and play essential roles in cancer progression and metastasis. Genetic mutations will occur randomly in any nucleotides of one particular gene and the comprehensive determination of DNA mutations is thus very difficult and time-consuming. In contrast, aberrant DNA hypermethylation usually takes place in defined CpG Islands within the regulatory region of the genes and it is much more convenient to detect DNA methylation in a quantitatively manner. In addition, DNA methylation can be amplified without any amplification bias from a single cell which allows investigating tumor heterogeneity. Due to such advantages over genetic mutations, epigenetic biomarkers have been intensively investigated for personalized medicine.

Epigenetic mediated gene silencing in tumor metastasis, recurrence and resistance

Aberrant DNA methylation is observed in all types of cancer, in which they affect a large number of genes related to tumor metastasis and recurrence. Although the list of aberrantly epigenetically regulated genes continues to grow in cancer progression, their potential role in risk assessment of cancer metastasis is obscure. More studies into the mechanism and consequence of demethylation are required before the cancer epigenome can be safely manipulated with therapeutics as a treatment modality. Recent study showed that tumor exosomes contains double standard DNA and it represents the entire genome and reflects mutational status . Interestingly, the amount of methylated DNA derived from tumor exosomes is similar to genomic DNA. Until now, however, a comprehensive characterization of ctDNA and exoDNA in cancer patients has not been conducted.