Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics

X. Li, H.E. Francies, M. Secrier, J. Perner, A. Miremadi, N. Galeano-Dalmau, W.J. Barendt, L. Letchford, G.M. Leyden, E.K. Goffin, A. Barthorpe, H. Lightfoot, E. Chen, J. Gilbert, A. Noorani, G. Devonshire, L. Bower, A. Grantham, S. MacRae, N. GrehanD.C. Wedge, R.C. Fitzgerald, M.J. Garnett

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalNature Communications
Early online date30 Jul 2018
DOIs
Publication statusPublished - 2018

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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