Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics
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Authors
Li, Xiaodun
Francies, Hayley
Secrier, Maria
Pener, Juliane
Miremadi, Ahmad
Galeano-Dalmau, Núria
Barendt, William
Letchford, Laura
Leyden, Genevieve
Goffin, Emma
Barthorpe, Andrew
Lightfoot, Howard
Chen, Elisabeth
Gilbert, James
Noorani, Ayesha
Devonshire, Ginny
Bower, Lawrence
Grantham, Amber
MacRae, Shona
Grehan, Nicola
Wedge, David
Garnett, Mathew
Publication Date
2018-07-30Journal Title
Nature Communications
ISSN
2041-1723
Publisher
Springer Nature
Volume
9
Number
2983
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Li, X., Francies, H., Secrier, M., Pener, J., Miremadi, A., Galeano-Dalmau, N., Barendt, W., et al. (2018). Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nature Communications, 9 (2983) https://doi.org/10.1038/s41467-018-05190-9
Abstract
Esophageal adenocarcinoma (EAC) incidence is increasing while 5-year survival rates remain less than 15%. A lack of experimental models has hampered progress. We have generated clinically annotated EAC organoid cultures that recapitulate the morphology, genomic and transcriptomic landscape of the primary tumor including point mutations, copy number alterations and mutational signatures. Karyotyping has confirmed polyclonality reflecting the clonal architecture of the primary and subclones underwent clonal selection associated with driver gene status. Medium throughput drug sensitivity testing demonstrates the potential of targeting receptor tyrosine kinases and downstream mediators. EAC organoid cultures provide a pre-clinical tool for studies of clonal evolution and precision therapeutics.
Keywords
Adenocarcinoma, Aged, Aged, 80 and over, Clonal Evolution, DNA Copy Number Variations, DNA Mutational Analysis, Drug Screening Assays, Antitumor, Esophageal Neoplasms, Female, Humans, Inhibitory Concentration 50, Karyotyping, Male, Middle Aged, Mutation, Organoids, Precision Medicine, Receptor Protein-Tyrosine Kinases, Sequence Analysis, RNA, Transcriptome
Sponsorship
Cancer Research UK (22131)
NIHR Clinical Research Network Eastern (via Cambridge University Hospitals NHS Foundation Trust (CUH)) (876523)
Medical Research Council (MC_UU_12022/2)
Identifiers
External DOI: https://doi.org/10.1038/s41467-018-05190-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/285967
Rights
Attribution 4.0 International, Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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