Epigenetic alteration means a heritable change that does not affect the DNA sequence but results in a change in gene expression. DNA methylation is a process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. In mammals DNA methylation is essential for normal development and is associated with a number of key processes including genomic imprinting, X-chromosome inactivation, repression of transposable elements, aging, and carcinogenesis. In addition, abnormal DNA methylation, unlike genetic alteration, can be detected in early cancer or precancerous cancer. DNA methylation has the advantages such as high cancer specificity, structural stability over proteins and RNA, and DNA amplification by PCR. DNA methylation is therefore recognized as the best cancer early diagnosis biomarker.

• The most ideal methylation biomarkers for early cancer detection are biomarkers that are normally not at all methylated, where methylation occurs in the early stages of cancer, and is constantly maintained, regardless of the cancer stage. In other words, they are biomarkers where methylation can be detected using liquid biopsies (body fluids) in early cancers, and even in precancerous stages
• Furthermore, because biomarkers usually exist in minute amounts in bodily fluids, ideal biomarkers should be detected using precise methods.

• Abnormal DNA methylation frequently occurs from the early stages of cancer, and is highly specific to solid cancers.
• Abnormal DNA methylation will tend to occur at common sites in all patients with the same type of cancer.
• Moreover, DNA methylation is change on the DNA with high stability. This indicates that the well-established method of nucleic acid amplification known as PCR can be used to selectively amplify the methylated DNA, making detection possible in body fluids, even in early cancer stages.
• DNA methylation biomarkers have several advantages over the conventionally known protein, RNA, and genetic markers, from the aspect of early detection.