Molecular landscape and functional characterization of centrosome amplification in ovarian cancer

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. Reinius, Lena Morrill Gavarró, Anne-Marie Mes-Masson, Darren Ennis, David Millan, Aoisha Hoyle, Iain A. McNeish, Mercedes Jimenez-Linan, Filipe Correia Martins, Julia Tischer, Maria Vias and James D. Brenton ()
Additional contact information
Carolin M. Sauer: University of Cambridge, Li Ka Shing Centre, Robinson Way
James A. Hall: University of Cambridge, Li Ka Shing Centre, Robinson Way
Dominique-Laurent Couturier: University of Cambridge, Li Ka Shing Centre, Robinson Way
Thomas Bradley: University of Cambridge, Li Ka Shing Centre, Robinson Way
Anna M. Piskorz: University of Cambridge, Li Ka Shing Centre, Robinson Way
Jacob Griffiths: University of Cambridge, Li Ka Shing Centre, Robinson Way
Ashley Sawle: University of Cambridge, Li Ka Shing Centre, Robinson Way
Matthew D. Eldridge: University of Cambridge, Li Ka Shing Centre, Robinson Way
Philip Smith: University of Cambridge, Li Ka Shing Centre, Robinson Way
Karen Hosking: University of Cambridge
Marika A. V. Reinius: University of Cambridge, Li Ka Shing Centre, Robinson Way
Lena Morrill Gavarró: University of Cambridge, Li Ka Shing Centre, Robinson Way
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
Julia Tischer: University of Cambridge, Li Ka Shing Centre, Robinson Way
Maria Vias: University of Cambridge, Li Ka Shing Centre, Robinson Way
James D. Brenton: University of Cambridge, Li Ka Shing Centre, Robinson Way

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41840-3

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