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Quantitative assessment of DNA methylation: potential applications for disease diagnosis, classification, and prognosis in clinical settings

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Abstract

Deregulation of the epigenome is now recognized as a major mechanism involved in the development and progression of human diseases such as cancer. As opposed to the irreversible nature of genetic events, which introduce changes in the primary DNA sequence, epigenetic modifications are reversible and leave the original DNA sequence intact. There is now evidence that the epigenetic landscape in humans undergoes modifications as the result of normal aging, with older individuals exhibiting higher levels of promoter hypermethylation compared to younger ones. Thus, it has been proposed that the higher incidence of certain disease in older individuals might be, in part, a consequence of an inherent change in the control and regulation of the epigenome. These observations are of remarkable clinical significance since the aberrant epigenetic changes characteristic of disease provide a unique platform for the development of new therapeutic approaches. In this review, we address the significance of DNA methylation changes that result or lead to disease, occur with aging, or may be the result of environmental exposure. We provide a detailed description of quantitative techniques currently available for the detection and analysis of DNA methylation and provide a comprehensive framework that may allow for the incorporation of protocols which include DNA methylation as a tool for disease diagnosis and classification, which could lead to the tailoring of therapeutic approaches designed to individual patient needs.

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Acknowledgements

The authors would like to thank Dr. Laura J. Rush and Dr. Joseph Costello for their input and critical reading of this manuscript. The work is supported in part by National Institute of Health grants CA93548 and DE13123, the Leukemia and Lymphoma Society, and the foundation Women Against Lung Cancer.

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Authors and Affiliations

  1. Division of Human Cancer Genetics, Department of Molecular Genetics, The Ohio State University, Columbus, OH, 43210, USA

    Romulo Martin Brena

  2. Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH, 43210, USA

    Romulo Martin Brena, Tim Hui-Ming Huang & Christoph Plass

  3. Division of Human Cancer Genetics, Medical Research Facility Room 464A, 420 West 12th Ave, Columbus, OH, 43210, USA

    Christoph Plass

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  1. Romulo Martin Brena
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  2. Tim Hui-Ming Huang
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Correspondence to Christoph Plass.

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Brena, R.M., Huang, T.HM. & Plass, C. Quantitative assessment of DNA methylation: potential applications for disease diagnosis, classification, and prognosis in clinical settings. J Mol Med 84, 365–377 (2006). https://doi.org/10.1007/s00109-005-0034-0

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  • DOI: https://doi.org/10.1007/s00109-005-0034-0

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