Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics
Open accessAbstract
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 of organoid cultures has confirmed polyclonality reflecting the clonal architecture of the primary tumor. Furthermore, 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.
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RNAseq has shown that organoids have gene expression profiles similar to the tumors from which they were established across many tumor types, including bladder and esophageal cancer.
“This has been shown by RNAseq on many tumor types including bladder cancer128 and esophageal cancer129 amongst others.”
From Organoids (2022) · cites this paper as [128]
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- Authors
- Li, X., Francies, H. E., Secrier, M., Perner, J., Miremadi, A., Galeano-Dalmau, N., Barendt, W. J., Letchford, L., Leyden, G. M., Goffin, E. K., Barthorpe, A., Lightfoot, H., Chen, E., Gilbert, J., Noorani, A., Devonshire, G., Bower, L., Grantham, A., MacRae, S., Grehan, N., Wedge, D. C., Fitzgerald, R. C., & Garnett, M. J.
- Affiliations
- University of Cambridge (GB)
- Wellcome Sanger Institute (GB)
- AstraZeneca (United Kingdom) (GB)
- Cancer Research UK (GB)
- University of Oxford (GB)
- Corresponding author
- Fitzgerald, Rebecca C.
- ORCID
- Venue
- Nature Communications
- Published
- 2018-07-30
- Volume
- 9
- Issue
- 1
- Pages
- 2983-2983
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6065407
- OpenAlex
- W2884074563
- Cited by
- 316
- References
- 50
- Citations by year
- 2026: 25 · 2025: 31 · 2024: 56 · 2023: 46 · 2022: 43 · 2021: 57 · 2020: 36 · 2019: 20 · 2018: 2
- FWCI
- 29.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Medical Research Council (RG84369)
- DH | National Institute for Health Research (RG67258)
- Cancer Research UK (RG66287, C44943/A22536)
- Wellcome Trust (102696)
- EIF | Stand Up To Cancer (SU2C-AACR-DT1213)
- Topics
- Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- esophageal adenocarcinoma, organoid culture, tumor heterogeneity, clonal evolution, polyclonality, subclonal selection, driver genes, mutational signatures, copy number alterations, drug susceptibility testing, receptor tyrosine kinase, precision therapy
- MeSH terms
- Adenocarcinoma, Aged, Aged, 80 and over, DNA Mutational Analysis, Drug Screening Assays, Antitumor, Esophageal Neoplasms, Female, Humans, Karyotyping, Male, Middle Aged, Mutation, Organoids, Sequence Analysis, RNA, Inhibitory Concentration 50, Receptor Protein-Tyrosine Kinases, DNA Copy Number Variations, Precision Medicine, Transcriptome, Clonal Evolution
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