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@article{Nastase:2020:10.1101/2020.01.23.20018523,
author = {Nastase, A and Mandal, A and Lu, SK and Anbunathan, H and Morris-Rosendahl, D and Zhang, YZ and Sun, X-M and Gennatas, S and Rintoul, RC and Edwards, M and Bowman, A and Chernova, T and Benepal, T and Lim, E and Taylor, AN and Nicholson, AG and Popat, S and Willis, AE and MacFarlane, M and Lathrop, M and Bowcock, AM and Moffatt, MF and Cookson, WOCM},
doi = {10.1101/2020.01.23.20018523},
title = {Integrated genomics identify novel immunotherapy targets for malignant mesothelioma},
url = {http://dx.doi.org/10.1101/2020.01.23.20018523},
year = {2020}
}
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TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited effective therapies.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In order to identify therapeutic targets, we integrated SNP genotyping, sequencing and transcriptomics from tumours and low-passage patient-derived cells.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Previously unrecognised losses of <jats:italic>SUFU</jats:italic> locus (10q24.32), observed in 21% of 118 tumours, resulted in disordered expression of transcripts from Hedgehog pathways and the T-cell synapse including <jats:italic>VISTA</jats:italic>. Co-deletion of Interferon Type I genes and <jats:italic>CDKN2A</jats:italic> was present in half of tumours and was a predictor of poor survival. We also found previously unrecognised deletions in <jats:italic>RB1</jats:italic> in 26% of cases and show sub-micromolar responses to downstream PLK1, CHEK1 and Aurora Kinase inhibitors in primary MPM cells. Defects in Hippo pathways that included <jats:italic>RASSF7</jats:italic> amplification and <jats:italic>NF2</jats:italic> or <jats:italic>LATS1</jats:italic>/2 mutations were present in 50% of tumours and were accompanied by micromolar responses to the YAP1 inhibitor Verteporfin.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Our results suggest new therapeutic avenues in MPM and provide targets and biomarkers for immunotherapy.</jats:p></jats:sec>
AU  - Nastase,A
AU  - Mandal,A
AU  - Lu,SK
AU  - Anbunathan,H
AU  - Morris-Rosendahl,D
AU  - Zhang,YZ
AU  - Sun,X-M
AU  - Gennatas,S
AU  - Rintoul,RC
AU  - Edwards,M
AU  - Bowman,A
AU  - Chernova,T
AU  - Benepal,T
AU  - Lim,E
AU  - Taylor,AN
AU  - Nicholson,AG
AU  - Popat,S
AU  - Willis,AE
AU  - MacFarlane,M
AU  - Lathrop,M
AU  - Bowcock,AM
AU  - Moffatt,MF
AU  - Cookson,WOCM
DO  - 10.1101/2020.01.23.20018523
PY  - 2020///
TI  - Integrated genomics identify novel immunotherapy targets for malignant mesothelioma
UR  - http://dx.doi.org/10.1101/2020.01.23.20018523
UR  - https://doi.org/10.1101/2020.01.23.20018523
ER  -
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