A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity

Louisa Nelson, Anthony Tighe, Anya Golder, Samantha Littler, Bjorn Bakker, Daniela Moralli, Syed Murtuza Baker, Ian J. Donaldson, Diana C. J. Spierings, René Wardenaar, Bethanie Neale, George J. Burghel, Brett Winter-Roach, Richard Edmondson, Andrew R. Clamp, Gordon C. Jayson, Sudha Desai, Catherine M. Green, Andy Hayes, Floris Foijer, Robert D. Morgan and Stephen S. Taylor ()
Additional contact information
Louisa Nelson: University of Manchester, Manchester Cancer Research Centre
Anthony Tighe: University of Manchester, Manchester Cancer Research Centre
Anya Golder: University of Manchester, Manchester Cancer Research Centre
Samantha Littler: University of Manchester, Manchester Cancer Research Centre
Bjorn Bakker: University of Groningen, University Medical Center Groningen
Daniela Moralli: University of Oxford, Roosevelt Drive
Syed Murtuza Baker: University of Manchester
Ian J. Donaldson: University of Manchester
Diana C. J. Spierings: University of Groningen, University Medical Center Groningen
René Wardenaar: University of Groningen, University Medical Center Groningen
Bethanie Neale: Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre
George J. Burghel: Central Manchester NHS Foundation Trust
Brett Winter-Roach: The Christie NHS Foundation Trust
Richard Edmondson: University of Manchester, Manchester Cancer Research Centre
Andrew R. Clamp: The Christie NHS Foundation Trust
Gordon C. Jayson: University of Manchester, Manchester Cancer Research Centre
Sudha Desai: The Christie NHS Foundation Trust
Catherine M. Green: University of Oxford, Roosevelt Drive
Andy Hayes: University of Manchester
Floris Foijer: University of Groningen, University Medical Center Groningen
Robert D. Morgan: University of Manchester, Manchester Cancer Research Centre
Stephen S. Taylor: University of Manchester, Manchester Cancer Research Centre

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract High-grade serous ovarian carcinoma is characterised by TP53 mutation and extensive chromosome instability (CIN). Because our understanding of CIN mechanisms is based largely on analysing established cell lines, we developed a workflow for generating ex vivo cultures from patient biopsies to provide models that support interrogation of CIN mechanisms in cells not extensively cultured in vitro. Here, we describe a “living biobank” of ovarian cancer models with extensive replicative capacity, derived from both ascites and solid biopsies. Fifteen models are characterised by p53 profiling, exome sequencing and transcriptomics, and karyotyped using single-cell whole-genome sequencing. Time-lapse microscopy reveals catastrophic and highly heterogeneous mitoses, suggesting that analysis of established cell lines probably underestimates mitotic dysfunction in advanced human cancers. Drug profiling reveals cisplatin sensitivities consistent with patient responses, demonstrating that this workflow has potential to generate personalized avatars with advantages over current pre-clinical models and the potential to guide clinical decision making.

Date: 2020
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DOI: 10.1038/s41467-020-14551-2

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