Integrated genomics point to immune vulnerabilities in pleural mesothelioma.

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dc.creatorNastase, Anca
dc.creatorMandal, Amit
dc.creatorLu, Shir Kiong
dc.creatorAnbunathan, Hima
dc.creatorMorris-Rosendahl, Deborah
dc.creatorZhang, Yu Zhi
dc.creatorSun, Xiao-Ming
dc.creatorGennatas, Spyridon
dc.creatorRintoul, Robert C
dc.creatorEdwards, Matthew
dc.creatorBowman, Alex
dc.creatorChernova, Tatyana
dc.creatorBenepal, Tim
dc.creatorLim, Eric
dc.creatorTaylor, Anthony Newman
dc.creatorNicholson, Andrew G
dc.creatorPopat, Sanjay
dc.creatorWillis, Anne E
dc.creatorMacFarlane, Marion
dc.creatorLathrop, Mark
dc.creatorBowcock, Anne M
dc.creatorMoffatt, Miriam F
dc.creatorCookson, William O C M
dc.date2021-10-30T01:13:20Z
dc.date2021-10-30T01:13:20Z
dc.date2021-09-27
dc.date2021-10-30T01:13:19Z
dc.date.accessioned2026-08-02T20:18:00Z
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.descriptionPleural 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.formatapplication/pdf
dc.identifier2045-2322
dc.identifierPMC8476593
dc.identifier34580349
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/330095
dc.identifier10.17863/CAM.77539
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/85141
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rightshttps://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

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