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Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer

Author

Listed:
  • Muhammed Murtaza

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge
    Center for Noninvasive Diagnostics, Translational Genomics Research Institute
    Mayo Clinic Center for Individualized Medicine)

  • Sarah-Jane Dawson

    (Cancer Research UK Cambridge Institute, University of Cambridge
    Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre, and the Cambridge Experimental Cancer Medicine Centre
    Peter MacCallum Cancer Centre)

  • Katherine Pogrebniak

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge)

  • Oscar M. Rueda

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge)

  • Elena Provenzano

    (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre, and the Cambridge Experimental Cancer Medicine Centre
    Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust)

  • John Grant

    (Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust)

  • Suet-Feung Chin

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge)

  • Dana W. Y. Tsui

    (Cancer Research UK Cambridge Institute, University of Cambridge)

  • Francesco Marass

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge)

  • Davina Gale

    (Cancer Research UK Cambridge Institute, University of Cambridge)

  • H. Raza Ali

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge
    Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre, and the Cambridge Experimental Cancer Medicine Centre
    Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust)

  • Pankti Shah

    (Center for Noninvasive Diagnostics, Translational Genomics Research Institute)

  • Tania Contente-Cuomo

    (Center for Noninvasive Diagnostics, Translational Genomics Research Institute)

  • Hossein Farahani

    (BC Cancer Research Centre)

  • Karey Shumansky

    (BC Cancer Research Centre)

  • Zoya Kingsbury

    (Illumina, Inc., Chesterford Research Park)

  • Sean Humphray

    (Illumina, Inc., Chesterford Research Park)

  • David Bentley

    (Illumina, Inc., Chesterford Research Park)

  • Sohrab P. Shah

    (BC Cancer Research Centre)

  • Matthew Wallis

    (Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre, and the Cambridge Experimental Cancer Medicine Centre
    Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust)

  • Nitzan Rosenfeld

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge)

  • Carlos Caldas

    (Cancer Research UK Cambridge Institute, University of Cambridge
    University of Cambridge
    Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge University Hospital National Health Service Foundation Trust and National Institute for Health Research Cambridge Biomedical Research Centre, and the Cambridge Experimental Cancer Medicine Centre)

Abstract

Circulating tumour DNA analysis can be used to track tumour burden and analyse cancer genomes non-invasively but the extent to which it represents metastatic heterogeneity is unknown. Here we follow a patient with metastatic ER-positive and HER2-positive breast cancer receiving two lines of targeted therapy over 3 years. We characterize genomic architecture and infer clonal evolution in eight tumour biopsies and nine plasma samples collected over 1,193 days of clinical follow-up using exome and targeted amplicon sequencing. Mutation levels in the plasma samples reflect the clonal hierarchy inferred from sequencing of tumour biopsies. Serial changes in circulating levels of sub-clonal private mutations correlate with different treatment responses between metastatic sites. This comparison of biopsy and plasma samples in a single patient with metastatic breast cancer shows that circulating tumour DNA can allow real-time sampling of multifocal clonal evolution.

Suggested Citation

  • Muhammed Murtaza & Sarah-Jane Dawson & Katherine Pogrebniak & Oscar M. Rueda & Elena Provenzano & John Grant & Suet-Feung Chin & Dana W. Y. Tsui & Francesco Marass & Davina Gale & H. Raza Ali & Pankti, 2015. "Multifocal clonal evolution characterized using circulating tumour DNA in a case of metastatic breast cancer," Nature Communications, Nature, vol. 6(1), pages 1-6, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9760
    DOI: 10.1038/ncomms9760
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    Cited by:

    1. Benjamin Wölfl & Hedy te Rietmole & Monica Salvioli & Artem Kaznatcheev & Frank Thuijsman & Joel S. Brown & Boudewijn Burgering & Kateřina Staňková, 2022. "The Contribution of Evolutionary Game Theory to Understanding and Treating Cancer," Dynamic Games and Applications, Springer, vol. 12(2), pages 313-342, June.
    2. Smruthy Sivakumar & Dexter X. Jin & Hanna Tukachinsky & Karthikeyan Murugesan & Kimberly McGregor & Natalie Danziger & Dean Pavlick & Ole Gjoerup & Jeffrey S. Ross & Robert Harmon & Jon Chung & Brenna, 2022. "Tissue and liquid biopsy profiling reveal convergent tumor evolution and therapy evasion in breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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