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Nat Commun. 2018 Jul 30;9(1):2983. doi: 10.1038/s41467-018-05190-9.

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

Author information

1
MRC Cancer Unit, University of Cambridge, Cambridge, CB2 0XZ, UK.
2
Wellcome Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
3
Cancer Research UK Cambridge Institute, Cambridge, CB2 0RE, UK.
4
Oncology IMED, AstraZeneca, Chesterford, Cambridge, CB10 1XL, UK.
5
Cambridge University Hospitals NHS Trust, Cambridge, CB2 0QQ, UK.
6
Big Data Institute, University of Oxford, Oxford, OX3 7LF, UK.
7
Oxford NIHR Biomedical Research Centre, Oxford, OX4 2PG, UK.
8
MRC Cancer Unit, University of Cambridge, Cambridge, CB2 0XZ, UK. RCF29@mrc-cu.cam.ac.uk.
9
Cambridge University Hospitals NHS Trust, Cambridge, CB2 0QQ, UK. RCF29@mrc-cu.cam.ac.uk.

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.

PMID:
30061675
PMCID:
PMC6065407
DOI:
10.1038/s41467-018-05190-9
[Indexed for MEDLINE]
Free PMC Article

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