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Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value

Author

Listed:
  • Clare Stirzaker

    (Epigenetics Group, Garvan Institute of Medical Research
    St Vincent's Clinical School, University of NSW)

  • Elena Zotenko

    (Epigenetics Group, Garvan Institute of Medical Research
    St Vincent's Clinical School, University of NSW)

  • Jenny Z. Song

    (Epigenetics Group, Garvan Institute of Medical Research)

  • Wenjia Qu

    (Epigenetics Group, Garvan Institute of Medical Research)

  • Shalima S. Nair

    (Epigenetics Group, Garvan Institute of Medical Research
    St Vincent's Clinical School, University of NSW)

  • Warwick J. Locke

    (Epigenetics Group, Garvan Institute of Medical Research
    St Vincent's Clinical School, University of NSW)

  • Andrew Stone

    (Epigenetics Group, Garvan Institute of Medical Research
    St Vincent's Clinical School, University of NSW)

  • Nicola J. Armstong

    (Epigenetics Group, Garvan Institute of Medical Research
    School of Mathematics and Statistics, University of Sydney)

  • Mark D. Robinson

    (Epigenetics Group, Garvan Institute of Medical Research
    Swiss Institute of Bioinformatics and Institute of Molecular Life Sciences, University of Zurich)

  • Alexander Dobrovic

    (Translational Genomics & Epigenomics Laboratory, Olivia Newton-John Cancer Research Institute)

  • Kelly A. Avery-Kiejda

    (School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle)

  • Kate M. Peters

    (School of Chemistry and Molecular Biosciences, University of Queensland)

  • Juliet D. French

    (School of Chemistry and Molecular Biosciences, University of Queensland
    QIMR Berghofer Medical Research Institute)

  • Sandra Stein

    (Pathology Queensland, Princess Alexandra Hospital)

  • Darren J. Korbie

    (Australian Institute for Bioengineering and Nanotechnology, University of Queensland)

  • Matt Trau

    (School of Chemistry and Molecular Biosciences, University of Queensland
    Australian Institute for Bioengineering and Nanotechnology, University of Queensland)

  • John F. Forbes

    (School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle)

  • Rodney J. Scott

    (School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle
    Hunter Area Pathology Service and the Hunter Medical Research Institute, John Hunter Hospital)

  • Melissa A. Brown

    (School of Chemistry and Molecular Biosciences, University of Queensland)

  • Glenn D. Francis

    (Pathology Queensland, Princess Alexandra Hospital
    Australian Institute for Bioengineering and Nanotechnology, University of Queensland)

  • Susan J. Clark

    (Epigenetics Group, Garvan Institute of Medical Research
    St Vincent's Clinical School, University of NSW)

Abstract

Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple-negative breast cancer (TNBC) and matched normal samples. We identify differentially methylated regions (DMRs) enriched with promoters associated with transcription factor binding sites and DNA hypersensitive sites. Importantly, we stratify TNBCs into three distinct methylation clusters associated with better or worse prognosis and identify 17 DMRs that show a strong association with overall survival, including DMRs located in the Wilms tumour 1 (WT1) gene, bi-directional-promoter and antisense WT1-AS. Our data reveal that coordinated hypermethylation can occur in oestrogen receptor-negative disease, and that characterizing the epigenetic framework provides a potential signature to stratify TNBCs. Together, our findings demonstrate the feasibility of profiling the cancer methylome with limited archival tissue to identify regulatory regions associated with cancer.

Suggested Citation

  • Clare Stirzaker & Elena Zotenko & Jenny Z. Song & Wenjia Qu & Shalima S. Nair & Warwick J. Locke & Andrew Stone & Nicola J. Armstong & Mark D. Robinson & Alexander Dobrovic & Kelly A. Avery-Kiejda & K, 2015. "Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6899
    DOI: 10.1038/ncomms6899
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