Imperial College London
Portrait Picture

ProfessorIainMcNeish

Faculty of Medicine, Department of Surgery & Cancer

Chair in Oncology
 
 
 
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Contact

 

+44 (0)20 7594 2185i.mcneish Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

G036Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Walton:2017:10.1038/s41598-017-17119-1,
author = {Walton, JB and Farquharson, M and Mason, S and Port, J and Kruspig, B and Dowson, S and Stevenson, D and Murphy, D and Matzuk, M and Kim, J and Coffelt, S and Blyth, K and McNeish, IA},
doi = {10.1038/s41598-017-17119-1},
journal = {Scientific Reports},
title = {CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity.},
url = {http://dx.doi.org/10.1038/s41598-017-17119-1},
volume = {7},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Transplantable murine models of ovarian high grade serous carcinoma (HGSC) remain an important research tool. We previously showed that ID8, a widely-used syngeneic model of ovarian cancer, lacked any of the frequent mutations in HGSC, and used CRISPR/Cas9 gene editing to generate derivatives with deletions in Trp53 and Brca2. Here we have used one ID8 Trp53 -/- clone to generate further mutants, with additional mutations in Brca1, Pten and Nf1, all of which are frequently mutated or deleted in HGSC. We have also generated clones with triple deletions in Trp53, Brca2 and Pten. We show that ID8 Trp53 -/-;Brca1 -/- and Trp53 -/-;Brca2 -/- cells have defective homologous recombination and increased sensitivity to both platinum and PARP inhibitor chemotherapy compared to Trp53 -/-. By contrast, loss of Pten or Nf1 increases growth rate in vivo, and reduces survival following cisplatin chemotherapy in vivo. Finally, we have also targeted Trp53 in cells isolated from a previous transgenic murine fallopian tube carcinoma model, and confirmed that loss of p53 expression in this second model accelerates intraperitoneal growth. Together, these CRISPR-generated models represent a new and simple tool to investigate the biology of HGSC, and the ID8 cell lines are freely available to researchers.
AU  - Walton,JB
AU  - Farquharson,M
AU  - Mason,S
AU  - Port,J
AU  - Kruspig,B
AU  - Dowson,S
AU  - Stevenson,D
AU  - Murphy,D
AU  - Matzuk,M
AU  - Kim,J
AU  - Coffelt,S
AU  - Blyth,K
AU  - McNeish,IA
DO  - 10.1038/s41598-017-17119-1
PY  - 2017///
SN  - 2045-2322
TI  - CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity.
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-017-17119-1
UR  - http://hdl.handle.net/10044/1/54936
VL  - 7
ER  -
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