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Analysis of DNA methylation in cancer: location revisited

Nature Reviews Clinical Oncology volume 15, pages 459–466 (2018)Cite this article

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A Correction to this article was published on 30 April 2018

Abstract

Changes in DNA methylation in cancer have been heralded as promising targets for the development of powerful diagnostic, prognostic, and predictive biomarkers. Despite the existence of more than 14,000 scientific publications describing DNA methylation-based biomarkers and their clinical associations in cancer, only 14 of these biomarkers have been translated into a commercially available clinical test. Methodological and experimental obstacles are both major causes of this disparity, but the genomic location of a DNA methylation-based biomarker is an intrinsic and essential property that also has an important and often overlooked role. Here, we examine the importance of the location of DNA methylation for the development of cancer biomarkers, and take a detailed look at the genomic location and other relevant characteristics of the various biomarkers with commercially available tests. We also emphasize the value of publicly available databases for the development of DNA methylation-based biomarkers and the importance of accurate reporting of the full methodological details of research findings.

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Fig. 1: Success rates for the clinical implementation of cancer biomarkers.
Fig. 2: Genomic location of GSTP1 DNA methylation biomarkers.

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Acknowledgements

The work of the authors is supported financially by the Maag Lever Darm Stichting (MLDS, grant FP13-15), the Universiteitsfonds Limburg/SWOL, and an SU2C- DCS International Translational Cancer Research Dream Team Grant (Stand Up To Cancer (SU2C)-AACR- DT1415, MEDOCC). SU2C is a programme of the Entertainment Industry Foundation administered by the American Association for Cancer Research.

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Authors and Affiliations

  1. Department of Pathology, GROW — School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands

    Alexander Koch, Zheng Feng, Muriel X. Draht, Veerle Melotte, Kim M. Smits, Leander Van Neste & Manon van Engeland

  2. Division of Medical Oncology, Department of Internal Medicine, GROW — School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, Netherlands

    Sophie C. Joosten, Tim C. de Ruijter, Kim M. Smits & Jurgen Veeck

  3. Lung Cancer Program, University of Pittsburgh Cancer Institute, The Hillman Cancer Center, Pittsburgh, PA, USA

    James G. Herman

  4. BioBix: Laboratory of Bioinformatics and Computational Genomics, Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium

    Wim Van Criekinge

  5. Department of Mathematical Modelling, Statistics and Bioinformatics, Ghent University, Ghent, Belgium

    Tim De Meyer

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Contributions

A.K., S.C.J., and M.v.E. researched data for the article, all authors made a substantial contribution to discussion of content, A.K., S.C.J., and M.v.E. wrote the manuscript, and all authors reviewed and/or edited the manuscript before submission.

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Correspondence to Manon van Engeland.

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M.v.E. receives research funding from MDxHealth. W.V.C. is a consultant of MDxHealth. The other authors declare no competing interests.

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The Cancer Genome Atlas: https://cancergenome.nih.gov/ The International Cancer Genome Consortium: http://icgc.org/

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Koch, A., Joosten, S.C., Feng, Z. et al. Analysis of DNA methylation in cancer: location revisited. Nat Rev Clin Oncol 15, 459–466 (2018). https://doi.org/10.1038/s41571-018-0004-4

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