Author
Listed:
- Xiaodun Li
(MRC Cancer Unit, University of Cambridge)
- Hayley E. Francies
(Wellcome Sanger Institute, Hinxton)
- Maria Secrier
(Cancer Research UK Cambridge Institute
Oncology IMED, AstraZeneca, Chesterford)
- Juliane Perner
(Cancer Research UK Cambridge Institute)
- Ahmad Miremadi
(Cambridge University Hospitals NHS Trust)
- Núria Galeano-Dalmau
(MRC Cancer Unit, University of Cambridge)
- William J. Barendt
(Wellcome Sanger Institute, Hinxton)
- Laura Letchford
(Wellcome Sanger Institute, Hinxton)
- Genevieve M. Leyden
(Wellcome Sanger Institute, Hinxton)
- Emma K. Goffin
(Wellcome Sanger Institute, Hinxton)
- Andrew Barthorpe
(Wellcome Sanger Institute, Hinxton)
- Howard Lightfoot
(Wellcome Sanger Institute, Hinxton)
- Elisabeth Chen
(Wellcome Sanger Institute, Hinxton)
- James Gilbert
(Wellcome Sanger Institute, Hinxton)
- Ayesha Noorani
(MRC Cancer Unit, University of Cambridge)
- Ginny Devonshire
(Cancer Research UK Cambridge Institute)
- Lawrence Bower
(Cancer Research UK Cambridge Institute)
- Amber Grantham
(MRC Cancer Unit, University of Cambridge)
- Shona MacRae
(MRC Cancer Unit, University of Cambridge)
- Nicola Grehan
(Cambridge University Hospitals NHS Trust)
- David C. Wedge
(Big Data Institute, University of Oxford
Oxford NIHR Biomedical Research Centre)
- Rebecca C. Fitzgerald
(MRC Cancer Unit, University of Cambridge
Cambridge University Hospitals NHS Trust)
- Mathew J. Garnett
(Wellcome Sanger Institute, Hinxton)
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.
Suggested Citation
Xiaodun Li & Hayley E. Francies & Maria Secrier & Juliane Perner & Ahmad Miremadi & Núria Galeano-Dalmau & William J. Barendt & Laura Letchford & Genevieve M. Leyden & Emma K. Goffin & Andrew Barthorp, 2018.
"Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics,"
Nature Communications, Nature, vol. 9(1), pages 1-13, December.
Handle:
RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05190-9
DOI: 10.1038/s41467-018-05190-9
Download full text from publisher
Citations
Citations are extracted by the
CitEc Project, subscribe to its
RSS feed for this item.
Cited by:
- Marjan M. Naeini & Felicity Newell & Lauren G. Aoude & Vanessa F. Bonazzi & Kalpana Patel & Guy Lampe & Lambros T. Koufariotis & Vanessa Lakis & Venkateswar Addala & Olga Kondrashova & Rebecca L. John, 2023.
"Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy,"
Nature Communications, Nature, vol. 14(1), pages 1-17, December.
- Alvin Wei Tian Ng & Dylan Peter McClurg & Ben Wesley & Shahriar A. Zamani & Emily Black & Ahmad Miremadi & Olivier Giger & Rogier ten Hoopen & Ginny Devonshire & Aisling M. Redmond & Nicola Grehan & S, 2024.
"Disentangling oncogenic amplicons in esophageal adenocarcinoma,"
Nature Communications, Nature, vol. 15(1), pages 1-13, December.
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05190-9. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.