IMR Press / FBL / Volume 21 / Issue 2 / DOI: 10.2741/4399

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


DNA methylation at enhancer regions: Novel avenues for epigenetic biomarker development

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1 Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3
2 Interdisciplinary Oncology Program, Faculty of Medicine, University of British Columbia, 675 W 10th Avenue Vancouver, British Columbia, Canada, V5Z 1L3
3 Honours Biotechnology Program, Department of Microbiology and Immunology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada, V6T 1Z3
4 Department of Surgery, University of British Columbia, 910 W 10th Avenue, Vancouver, British Columbia, Canada, V5Z 4E3
Front. Biosci. (Landmark Ed) 2016, 21(2), 430–446;
Published: 1 January 2016

Biomarkers are molecules or features which can provide clinically-relevant information about a particular disease state, thus providing useful tools for oncologists. Recently, a number of studies have demonstrated that DNA methylation holds great promise as a novel source of cancer biomarkers. Although promoter regions have been the focus of most investigations thus far, mounting evidence demonstrates that enhancer sequences also undergo extensive differential methylation in cancer cells. Moreover, enhancer methylation correlates with target gene expression better than promoter methylation, providing unexplored strategies for biomarker development. Here, we review important considerations associated with the clinical analysis of DNA methylation at distal regulatory regions. Notably, we highlight emerging literature addressing the methylation status of enhancers in development and cancer, and subsequently discuss how enhancer methylation can be exploited to guide disease management. While acknowledging current limitations, we propose that the methylation state of enhancer regions has the potential to headline the next generation of epigenetic biomarkers.

DNA Methylation
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