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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 publication




Journal article


Nature communications

Publication Date





MRC Cancer Unit, University of Cambridge, Cambridge, CB2 0XZ, UK.


Organoids, Humans, Adenocarcinoma, Esophageal Neoplasms, Receptor Protein-Tyrosine Kinases, Drug Screening Assays, Antitumor, Karyotyping, DNA Mutational Analysis, Sequence Analysis, RNA, Inhibitory Concentration 50, Mutation, Aged, Aged, 80 and over, Middle Aged, Female, Male, DNA Copy Number Variations, Transcriptome, Clonal Evolution, Precision Medicine