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dc.contributor.authorHolme, Hen_US
dc.contributor.authorGulati, Aen_US
dc.contributor.authorBrough, Ren_US
dc.contributor.authorFleuren, EDGen_US
dc.contributor.authorBajrami, Ien_US
dc.contributor.authorCampbell, Jen_US
dc.contributor.authorChong, IYen_US
dc.contributor.authorCosta-Cabral, Sen_US
dc.contributor.authorElliott, Ren_US
dc.contributor.authorFenton, Ten_US
dc.contributor.authorFrankum, Jen_US
dc.contributor.authorJones, SEen_US
dc.contributor.authorMenon, Men_US
dc.contributor.authorMiller, Ren_US
dc.contributor.authorPemberton, HNen_US
dc.contributor.authorPostel-Vinay, Sen_US
dc.contributor.authorRafiq, Ren_US
dc.contributor.authorSelfe, JLen_US
dc.contributor.authorvon Kriegsheim, Aen_US
dc.contributor.authorMunoz, AGen_US
dc.contributor.authorRodriguez, Jen_US
dc.contributor.authorShipley, Jen_US
dc.contributor.authorvan der Graaf, WTAen_US
dc.contributor.authorWilliamson, CTen_US
dc.contributor.authorRyan, CJen_US
dc.contributor.authorPettitt, Sen_US
dc.contributor.authorAshworth, Aen_US
dc.contributor.authorStrauss, SJen_US
dc.contributor.authorLord, CJen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-07-31T10:42:03Z
dc.date.issued2018-07-13en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30006631en_US
dc.identifier10.1038/s41598-018-29043-zen_US
dc.identifier.citationSci Rep, 2018, 8 (1), pp. 10614 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2226
dc.identifier.eissn2045-2322en_US
dc.identifier.doi10.1038/s41598-018-29043-zen_US
dc.description.abstractOsteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygosity (LOH) patterns reminiscent of BRCA1 or BRCA2 mutant tumours. This raises the possibility that PARP inhibitors (PARPi), used to treat BRCA1/2 mutant cancers, could be used to target OS. Using high-throughput drug sensitivity screening we generated chemosensitivity profiles for 79 small molecule inhibitors, including three clinical PARPi. Drug screening was performed in 88 tumour cell lines, including 18 OS TCLs. This identified known sensitivity effects in OS TCLs, such as sensitivity to FGFR inhibitors. When compared to BRCA1/2 mutant TCLs, OS TCLs, with the exception of LM7, were PARPi resistant, including those with previously determined BRCAness LoH profiles. Post-screen validation experiments confirmed PARPi sensitivity in LM7 cells as well as a defect in the ability to form nuclear RAD51 foci in response to DNA damage. LM7 provides one OS model for the study of PARPi sensitivity through a potential defect in RAD51-mediated DNA repair. The drug sensitivity dataset we generated in 88 TCLs could also serve as a resource for the study of drug sensitivity effects in OS.en_US
dc.format.extent10614 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleChemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-07-02en_US
rioxxterms.versionofrecord10.1038/s41598-018-29043-zen_US
rioxxterms.licenseref.startdate2018-07-13en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfSci Repen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical and Translational Sarcoma
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Gene Function
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology
pubs.publication-statusPublished onlineen_US
pubs.volume8en_US
pubs.embargo.termsNot knownen_US
icr.researchteamClinical and Translational Sarcomaen_US
icr.researchteamGene Functionen_US
icr.researchteamSarcoma Molecular Pathologyen_US
dc.contributor.icrauthorShipley, Janeten_US
dc.contributor.icrauthorLord, Christopheren_US
dc.contributor.icrauthorSelfe, Joannaen_US
dc.contributor.icrauthorCampbell, Jamesen_US
dc.contributor.icrauthorPettitt, Stephenen_US
dc.contributor.icrauthorvan der Graaf, Wilhelminaen_US


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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/