Imperial College London
Alternate

DrSanjayPopat

Faculty of Medicine, National Heart & Lung Institute

Reader in Cancer Medicine
 
 
 
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Contact

 

+44 (0)20 7808 2132s.popat Website

 
 
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Location

 

Royal Marsden HospitalThe Royal Marsden Hospital

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Summary

 

Publications

Citation

BibTex format

@article{Nastase:2021:10.1038/s41598-021-98414-w,
author = {Nastase, A and Mandal, A and Lu, SK and Abunathan, H and Morris-Rosendahl, D and Zhand, YZ and Sun, X-M and Gennatas, S and Rintoul, R and Edwards, M and Bowman, A and Chernova, T and Benepal, T and Lim, E and Newman, Taylor A and Nicholson, A and Popat, S and Willis, A and MacFarlane, M and Lathrop, M and Bowcock, A and Moffatt, M and Cookson, W},
doi = {10.1038/s41598-021-98414-w},
journal = {Scientific Reports},
title = {Integrated genomics point to immune vulnerabilities in pleural mesothelioma},
url = {http://dx.doi.org/10.1038/s41598-021-98414-w},
volume = {11},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pleural mesothelioma is an aggressive malignancy with limited effective therapies. In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells. Previously unrecognised deletions of SUFU locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including VISTA. Co-deletion of Interferon Type I genes and CDKN2A was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in RB1 in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary mesothelioma cells. Defects in Hippo pathways that included RASSF7 amplification and NF2 or LATS1/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin. Our results suggest new therapeutic avenues in mesothelioma and indicate targets and biomarkers for immunotherapy.
AU  - Nastase,A
AU  - Mandal,A
AU  - Lu,SK
AU  - Abunathan,H
AU  - Morris-Rosendahl,D
AU  - Zhand,YZ
AU  - Sun,X-M
AU  - Gennatas,S
AU  - Rintoul,R
AU  - Edwards,M
AU  - Bowman,A
AU  - Chernova,T
AU  - Benepal,T
AU  - Lim,E
AU  - Newman,Taylor A
AU  - Nicholson,A
AU  - Popat,S
AU  - Willis,A
AU  - MacFarlane,M
AU  - Lathrop,M
AU  - Bowcock,A
AU  - Moffatt,M
AU  - Cookson,W
DO  - 10.1038/s41598-021-98414-w
PY  - 2021///
SN  - 2045-2322
TI  - Integrated genomics point to immune vulnerabilities in pleural mesothelioma
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-021-98414-w
UR  - http://hdl.handle.net/10044/1/92153
VL  - 11
ER  -
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