Journal article
A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 3.6MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-020-14551-2
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 11
- Issue:
- 1
- Article number:
- 822
- Publication date:
- 2020-02-13
- Acceptance date:
- 2020-01-14
- DOI:
- EISSN:
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2041-1723
- ISSN:
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2041-1723
- Pmid:
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32054838
- Language:
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English
- Pubs id:
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1087785
- Local pid:
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pubs:1087785
- Deposit date:
-
2020-04-06
Terms of use
- Copyright holder:
- Nelson et al.
- Copyright date:
- 2020
- Rights statement:
- © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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