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

  • External authors:
  • Anya Golder
  • Samantha Littler
  • Bjorn Bakker
  • Daniela Moralli
  • Diana C J Spierings
  • Rene Wardenaar
  • Bethanie Neale
  • George Burghel
  • Brett Winter-Roach
  • Andrew Clamp
  • Gordon Jayson
  • Sudha Desai
  • Catherine M Green
  • Andrew Hayes
  • Floris Foijer
  • Robert Morgan
  • Stephen Taylor

Standard

A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity. / Nelson, Louisa; Tighe, Anthony; Golder, Anya; Littler, Samantha; Bakker, Bjorn ; Moralli, Daniela; Baker, Syed Murtuza; Donaldson, Ian; Spierings, Diana C J ; Wardenaar, Rene; Neale, Bethanie; Burghel, George; Winter-Roach, Brett; Edmondson, Richard; Clamp, Andrew; Jayson, Gordon; Desai, Sudha; Green , Catherine M ; Hayes, Andrew; Foijer, Floris ; Morgan, Robert; Taylor, Stephen.

In: Nature Communications, Vol. 11, No. 1, 822, 13.02.2020.

Research output: Contribution to journalArticlepeer-review

Harvard

Nelson, L, Tighe, A, Golder, A, Littler, S, Bakker, B, Moralli, D, Baker, SM, Donaldson, I, Spierings, DCJ, Wardenaar, R, Neale, B, Burghel, G, Winter-Roach, B, Edmondson, R, Clamp, A, Jayson, G, Desai, S, Green , CM, Hayes, A, Foijer, F, Morgan, R & Taylor, S 2020, 'A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity', Nature Communications, vol. 11, no. 1, 822. https://doi.org/10.1038/s41467-020-14551-2

APA

Nelson, L., Tighe, A., Golder, A., Littler, S., Bakker, B., Moralli, D., Baker, S. M., Donaldson, I., Spierings, D. C. J., Wardenaar, R., Neale, B., Burghel, G., Winter-Roach, B., Edmondson, R., Clamp, A., Jayson, G., Desai, S., Green , C. M., Hayes, A., ... Taylor, S. (2020). A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity. Nature Communications, 11(1), [822]. https://doi.org/10.1038/s41467-020-14551-2

Vancouver

Nelson L, Tighe A, Golder A, Littler S, Bakker B, Moralli D et al. A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity. Nature Communications. 2020 Feb 13;11(1). 822. https://doi.org/10.1038/s41467-020-14551-2

Author

Nelson, Louisa ; Tighe, Anthony ; Golder, Anya ; Littler, Samantha ; Bakker, Bjorn ; Moralli, Daniela ; Baker, Syed Murtuza ; Donaldson, Ian ; Spierings, Diana C J ; Wardenaar, Rene ; Neale, Bethanie ; Burghel, George ; Winter-Roach, Brett ; Edmondson, Richard ; Clamp, Andrew ; Jayson, Gordon ; Desai, Sudha ; Green , Catherine M ; Hayes, Andrew ; Foijer, Floris ; Morgan, Robert ; Taylor, Stephen. / A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity. In: Nature Communications. 2020 ; Vol. 11, No. 1.

Bibtex

@article{79403cc16efa4aff8a8c2a70c9b003f2,
title = "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 capcity, 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. ",
keywords = "Biological Specimen Banks, Chromosomal Instability, Drug Resistance, Neoplasm, Female, Gene Expression, Gene Expression Profiling, Histological Techniques/methods, Humans, Imaging, Three-Dimensional, In Situ Hybridization, Fluorescence, In Vitro Techniques, Karyotyping, Mitosis/genetics, Models, Biological, Mutation, Ovarian Neoplasms/drug therapy, Paclitaxel/pharmacology, Single-Cell Analysis, Time-Lapse Imaging, Tumor Suppressor Protein p53/genetics, Whole Exome Sequencing",
author = "Louisa Nelson and Anthony Tighe and Anya Golder and Samantha Littler and Bjorn Bakker and Daniela Moralli and Baker, {Syed Murtuza} and Ian Donaldson and Spierings, {Diana C J} and Rene Wardenaar and Bethanie Neale and George Burghel and Brett Winter-Roach and Richard Edmondson and Andrew Clamp and Gordon Jayson and Sudha Desai and Green, {Catherine M} and Andrew Hayes and Floris Foijer and Robert Morgan and Stephen Taylor",
year = "2020",
month = feb,
day = "13",
doi = "10.1038/s41467-020-14551-2",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Springer Nature",
number = "1",

}

RIS

TY - JOUR

T1 - A living biobank of ovarian cancer ex vivo models reveals profound mitotic heterogeneity

AU - Nelson, Louisa

AU - Tighe, Anthony

AU - Golder, Anya

AU - Littler, Samantha

AU - Bakker, Bjorn

AU - Moralli, Daniela

AU - Baker, Syed Murtuza

AU - Donaldson, Ian

AU - Spierings, Diana C J

AU - Wardenaar, Rene

AU - Neale, Bethanie

AU - Burghel, George

AU - Winter-Roach, Brett

AU - Edmondson, Richard

AU - Clamp, Andrew

AU - Jayson, Gordon

AU - Desai, Sudha

AU - Green , Catherine M

AU - Hayes, Andrew

AU - Foijer, Floris

AU - Morgan, Robert

AU - Taylor, Stephen

PY - 2020/2/13

Y1 - 2020/2/13

N2 - 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 capcity, 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.

AB - 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 capcity, 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.

KW - Biological Specimen Banks

KW - Chromosomal Instability

KW - Drug Resistance, Neoplasm

KW - Female

KW - Gene Expression

KW - Gene Expression Profiling

KW - Histological Techniques/methods

KW - Humans

KW - Imaging, Three-Dimensional

KW - In Situ Hybridization, Fluorescence

KW - In Vitro Techniques

KW - Karyotyping

KW - Mitosis/genetics

KW - Models, Biological

KW - Mutation

KW - Ovarian Neoplasms/drug therapy

KW - Paclitaxel/pharmacology

KW - Single-Cell Analysis

KW - Time-Lapse Imaging

KW - Tumor Suppressor Protein p53/genetics

KW - Whole Exome Sequencing

U2 - 10.1038/s41467-020-14551-2

DO - 10.1038/s41467-020-14551-2

M3 - Article

C2 - 32054838

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 822

ER -