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Molecular landscape and functional characterization of centrosome amplification in ovarian cancer

Author

Listed:
  • Carolin M. Sauer

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • James A. Hall

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Dominique-Laurent Couturier

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Thomas Bradley

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Anna M. Piskorz

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Jacob Griffiths

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Ashley Sawle

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Matthew D. Eldridge

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Philip Smith

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Karen Hosking

    (University of Cambridge)

  • Marika A. V. Reinius

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge
    Addenbrooke’s Hospital)

  • Lena Morrill Gavarró

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Anne-Marie Mes-Masson

    (Université de Montréal and Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM))

  • Darren Ennis

    (Imperial College London)

  • David Millan

    (Queen Elizabeth University Hospital)

  • Aoisha Hoyle

    (University Hospital Monklands. NHS Lanarkshire)

  • Iain A. McNeish

    (Imperial College London)

  • Mercedes Jimenez-Linan

    (Addenbrooke’s Hospital)

  • Filipe Correia Martins

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge
    Addenbrooke’s Hospital)

  • Julia Tischer

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • Maria Vias

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge)

  • James D. Brenton

    (University of Cambridge, Li Ka Shing Centre, Robinson Way
    University of Cambridge
    Addenbrooke’s Hospital)

Abstract

High-grade serous ovarian carcinoma (HGSOC) is characterised by poor outcome and extreme chromosome instability (CIN). Therapies targeting centrosome amplification (CA), a key mediator of chromosome missegregation, may have significant clinical utility in HGSOC. However, the prevalence of CA in HGSOC, its relationship to genomic biomarkers of CIN and its potential impact on therapeutic response have not been defined. Using high-throughput multi-regional microscopy on 287 clinical HGSOC tissues and 73 cell lines models, here we show that CA through centriole overduplication is a highly recurrent and heterogeneous feature of HGSOC and strongly associated with CIN and genome subclonality. Cell-based studies showed that high-prevalence CA is phenocopied in ovarian cancer cell lines, and that high CA is associated with increased multi-treatment resistance; most notably to paclitaxel, the commonest treatment used in HGSOC. CA in HGSOC may therefore present a potential driver of tumour evolution and a powerful biomarker for response to standard-of-care treatment.

Suggested Citation

  • Carolin M. Sauer & James A. Hall & Dominique-Laurent Couturier & Thomas Bradley & Anna M. Piskorz & Jacob Griffiths & Ashley Sawle & Matthew D. Eldridge & Philip Smith & Karen Hosking & Marika A. V. R, 2023. "Molecular landscape and functional characterization of centrosome amplification in ovarian cancer," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41840-3
    DOI: 10.1038/s41467-023-41840-3
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    References listed on IDEAS

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