Journal article
Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics
- 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 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 4.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-018-05190-9
Authors
- Publisher:
- Nature Publishing Group
- Journal:
- Nature Communications More from this journal
- Volume:
- 9
- Issue:
- 1
- Pages:
- 2983
- Publication date:
- 2018-07-30
- Acceptance date:
- 2018-06-22
- DOI:
- ISSN:
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2041-1723
- Pmid:
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30061675
- Language:
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English
- Keywords:
- Pubs id:
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pubs:892105
- UUID:
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uuid:74fe1904-22ce-4939-8f48-d8d276fa928c
- Local pid:
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pubs:892105
- Source identifiers:
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892105
- Deposit date:
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2018-08-02
Terms of use
- Copyright holder:
- Wedge et al
- Copyright date:
- 2018
- Notes:
- © The Author(s) 2018. 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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