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dc.contributor.authorNastase, Anca
dc.contributor.authorMandal, Amit
dc.contributor.authorLu, Shir Kiong
dc.contributor.authorAnbunathan, Hima
dc.contributor.authorMorris-Rosendahl, Deborah
dc.contributor.authorZhang, Yu Zhi
dc.contributor.authorSun, Xiao-Ming
dc.contributor.authorGennatas, Spyridon
dc.contributor.authorRintoul, Robert C
dc.contributor.authorEdwards, Matthew
dc.contributor.authorBowman, Alex
dc.contributor.authorChernova, Tatyana
dc.contributor.authorBenepal, Tim
dc.contributor.authorLim, Eric
dc.contributor.authorTaylor, Anthony Newman
dc.contributor.authorNicholson, Andrew G
dc.contributor.authorPopat, Sanjay
dc.contributor.authorWillis, Anne E
dc.contributor.authorMacFarlane, Marion
dc.contributor.authorLathrop, Mark
dc.contributor.authorBowcock, Anne M
dc.contributor.authorMoffatt, Miriam F
dc.contributor.authorCookson, William O C M
dc.date.accessioned2021-10-30T01:13:20Z
dc.date.available2021-10-30T01:13:20Z
dc.date.issued2021-09-27
dc.identifier.issn2045-2322
dc.identifier.otherPMC8476593
dc.identifier.other34580349
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330095
dc.descriptionFunder: Libor Fund grant from the UK Department of Health, by the British Lung Foundation and by the Asmarley Foundation
dc.descriptionFunder: Medical Research Council
dc.description.abstractPleural 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.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2045-2322
dc.sourcenlmid: 101563288
dc.titleIntegrated genomics point to immune vulnerabilities in pleural mesothelioma.
dc.typeArticle
dc.date.updated2021-10-30T01:13:19Z
prism.issueIdentifier1
prism.publicationNameScientific reports
prism.volume11
dc.identifier.doi10.17863/CAM.77539
rioxxterms.versionofrecord10.1038/s41598-021-98414-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMandal, Amit [0000-0002-2530-8103]
dc.contributor.orcidWillis, Anne E [0000-0002-1470-8531]


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International