Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics
| Autor: | Li, X, Francies, H, Secrier, M, Perner, J, Miremadi, A, Galeano-Dalmau, N, Barendt, W, Letchford, L, Leyden, G, Goffin, E, Barthorpe, A, Lightfoot, H, Chen, E, Gilbert, J, Noorani, A, Devonshire, G, Bower, L, Grantham, A, Macrae, S, Grehan, N, Wedge, D, Fitzgerald, R, Garnett, M |
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| Přispěvatelé: | Fitzgerald, Rebecca [0000-0002-3434-3568], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
DNA Copy Number Variations Esophageal Neoplasms Science DNA Mutational Analysis Adenocarcinoma Article Clonal Evolution Inhibitory Concentration 50 Humans Precision Medicine lcsh:Science Aged Aged 80 and over Manchester Cancer Research Centre Sequence Analysis RNA ResearchInstitutes_Networks_Beacons/mcrc Receptor Protein-Tyrosine Kinases Middle Aged Organoids Karyotyping Mutation lcsh:Q Female Drug Screening Assays Antitumor Transcriptome |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature Communications 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 2018, ' Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics ', Nature Communications . https://doi.org/10.1038/s41467-018-05190-9 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-05190-9 |
| Popis: | 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. Esophageal adenocarcinoma (EAC) has a poor 5-year survival rate and lacks robust preclinical models for use in research. Here, the authors show that newly derived organoids recapitulate the transcriptomic, genetic, and morphological landscape of the primary EAC tumors and provide a platform to test drug sensitivity and study tumor clonality. |
| Databáze: | OpenAIRE |
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