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Analysis of DNA Methylation in Clinical Samples: Methods and Applications

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Molecular Pathology in Cancer Research

Abstract

DNA methylation is the only level of epigenetic change that can be readily assessed in most clinical samples. However, DNA methylation assays are largely confined to specialised, often research-oriented laboratories. This arises from a number of factors including lack of standardisation of methodologies, difficulties in choosing a consensus region for analysis, and the requirement for expertise in the interpretation of what can often be complex results.

A large number of methodologies have been developed to measure DNA methylation. Most of these methodologies have limitations, particularly when biological samples are being tested. This is due to the multiple possible combinations of methylated CpG positions in the templates (epialleles), ranging from all CpG sites being methylated to just a few or none being methylated. In addition, DNA from clinical samples, like formalin-fixed paraffin-embedded tissues or plasma DNA, is fragmented necessitating further methodological adaptations.

Analysis of DNA methylation has entered the mainstream of ‘omics’ analysis with DNA methylation profiling being included with mutation profiling and gene expression analysis as part of comprehensive genomic analyses of cancer. However, integrating DNA methylation information into precision medicine remains a challenge.

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Acknowledgments

I acknowledge my colleagues in DNA methylation, both those whom I have cited and those whose contributions I have omitted due to lack of space. I would like to thank Thomas Mikeska and Basant Ebaid for helpful comments on several drafts. Funding underlying this work is from the National Breast Cancer Foundation of Australia (CG-10-04, CG-12-07, PS-15-048), Cancer Australia (ID 1009892), the Cancer Council of Victoria, and the Victorian Cancer Agency (TRP13025, TRP13026). The Olivia Newton-John Cancer Research Institute is supported by the Victorian Government Operational and Infrastructure Support Grant.

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  1. Translational Genomics and Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia

    Alexander Dobrovic

  2. School of Cancer Medicine, La Trobe University, Bundoora, VIC, Australia

    Alexander Dobrovic

  3. Department of Pathology, University of Melbourne, Parkville, VIC, Australia

    Alexander Dobrovic

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Correspondence to Alexander Dobrovic .

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  1. UQ Centre for Clinical Research, The Royal Brisbane and Women’s Hospital, University of Queensland and Pathology Queensland, Brisbane, Queensland, Australia

    Sunil R. Lakhani

  2. Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia

    Stephen B. Fox

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Dobrovic, A. (2016). Analysis of DNA Methylation in Clinical Samples: Methods and Applications. In: Lakhani, S., Fox, S. (eds) Molecular Pathology in Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-6643-1_12

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