IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7605.html
   My bibliography  Save this article

Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer

Author

Listed:
  • Matthew K.H. Hong

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

  • Geoff Macintyre

    (Centre for Neural Engineering, University of Melbourne
    Cancer Research UK Cambridge Institute, University of Cambridge
    Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne)

  • David C. Wedge

    (Cancer Genome Project, Wellcome Trust Sanger Institute)

  • Peter Van Loo

    (Cancer Genome Project, Wellcome Trust Sanger Institute
    KU Leuven
    Cancer Research UK London Research Institute)

  • Keval Patel

    (Cancer Research UK Cambridge Institute, University of Cambridge
    Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust)

  • Sebastian Lunke

    (Centre for Translational Pathology, University of Melbourne)

  • Ludmil B. Alexandrov

    (Cancer Genome Project, Wellcome Trust Sanger Institute
    Los Alamos National Laboratory)

  • Clare Sloggett

    (Victorian Life Sciences Computation Initiative, The University of Melbourne)

  • Marek Cmero

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital
    Centre for Neural Engineering, University of Melbourne
    Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne)

  • Francesco Marass

    (Cancer Research UK Cambridge Institute, University of Cambridge)

  • Dana Tsui

    (Cancer Research UK Cambridge Institute, University of Cambridge)

  • Stefano Mangiola

    (Centre for Neural Engineering, University of Melbourne)

  • Andrew Lonie

    (Victorian Life Sciences Computation Initiative, The University of Melbourne)

  • Haroon Naeem

    (Centre for Neural Engineering, University of Melbourne
    Diagnostic Genomics, NICTA, Victoria Research Laboratory, The University of Melbourne)

  • Nikhil Sapre

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

  • Pramit M. Phal

    (Royal Melbourne Hospital)

  • Natalie Kurganovs

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

  • Xiaowen Chin

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

  • Michael Kerger

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

  • Anne Y. Warren

    (University Cambridge Hospitals, Addenbrookes Hospital)

  • David Neal

    (Cancer Research UK Cambridge Institute, University of Cambridge
    Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust)

  • Vincent Gnanapragasam

    (Cancer Research UK Cambridge Institute, University of Cambridge
    Academic Urology Group, Addenbrookes Hospital, Cambridge University, Hospitals NHS Foundation Trust)

  • Nitzan Rosenfeld

    (Cancer Research UK Cambridge Institute, University of Cambridge)

  • John S. Pedersen

    (TissuPath Specialist Pathology
    Monash University Faculty of Medicine)

  • Andrew Ryan

    (TissuPath Specialist Pathology)

  • Izhak Haviv

    (Bar-Ilan University Medical School)

  • Anthony J. Costello

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

  • Niall M. Corcoran

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

  • Christopher M. Hovens

    (Royal Melbourne Hospital and University of Melbourne
    The Epworth Prostate Centre, Epworth Hospital)

Abstract

Tumour heterogeneity in primary prostate cancer is a well-established phenomenon. However, how the subclonal diversity of tumours changes during metastasis and progression to lethality is poorly understood. Here we reveal the precise direction of metastatic spread across four lethal prostate cancer patients using whole-genome and ultra-deep targeted sequencing of longitudinally collected primary and metastatic tumours. We find one case of metastatic spread to the surgical bed causing local recurrence, and another case of cross-metastatic site seeding combining with dynamic remoulding of subclonal mixtures in response to therapy. By ultra-deep sequencing end-stage blood, we detect both metastatic and primary tumour clones, even years after removal of the prostate. Analysis of mutations associated with metastasis reveals an enrichment of TP53 mutations, and additional sequencing of metastases from 19 patients demonstrates that acquisition of TP53 mutations is linked with the expansion of subclones with metastatic potential which we can detect in the blood.

Suggested Citation

  • Matthew K.H. Hong & Geoff Macintyre & David C. Wedge & Peter Van Loo & Keval Patel & Sebastian Lunke & Ludmil B. Alexandrov & Clare Sloggett & Marek Cmero & Francesco Marass & Dana Tsui & Stefano Mang, 2015. "Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7605
    DOI: 10.1038/ncomms7605
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7605
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7605?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7605. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.