Abstract
Colorectal cancers (CRCs) are thought to arise through accumulation of genetic and epigenetic alterations. CRC genomes exhibit dual-faceted DNA methylation abnormality, global hypomethylation with CpG island hypermethylation, and CRCs are classified into two groups based on whether their genomes exhibit microsatellite instability (MSI) or chromosomal instability (CIN). In addition, a subset of CRCs is characterized by concurrent hypermethylation of multiple CpG islands, known as the CpG island methylator phenotype (CIMP). Genomic instability and epigenetic alterations are tightly linked, and CRCs with MSI largely overlap CIMP-positive tumors, while CIN is associated with global DNA hypomethylation. Dysregulation of histone methylation and altered expression of histone modifying enzymes are also commonly observed in CRC, indicating their critical roles in CRC development. Evidence now suggests that DNA and histone methylation could potentially serve as biomarkers useful for CRC diagnosis, risk assessment and prediction of therapeutic effects and prognosis. Although many studies examining clinical applications are still at an early phase, it is anticipated that further investigation will lead to improved prevention and management of CRC.
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Acknowledgements
We thank Dr. William Goldman for editing the manuscript. This study was supported in part by Grants-in-Aid for Scientific Research (B) from the Japan Society for Promotion of Science (JSPS KAKENHI 15H04299, H. Suzuki).
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Suzuki, H., Yamamoto, E., Nakase, H., Sugai, T. (2017). DNA and Histone Methylation in Colon Cancer. In: Kaneda, A., Tsukada, Yi. (eds) DNA and Histone Methylation as Cancer Targets. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-59786-7_17
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