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dc.contributor.authorStone, TJen_US
dc.contributor.authorKeeley, Aen_US
dc.contributor.authorVirasami, Aen_US
dc.contributor.authorHarkness, Wen_US
dc.contributor.authorTisdall, Men_US
dc.contributor.authorIzquierdo Delgado, Een_US
dc.contributor.authorGutteridge, Aen_US
dc.contributor.authorBrooks, Ten_US
dc.contributor.authorKristiansen, Men_US
dc.contributor.authorChalker, Jen_US
dc.contributor.authorWilkhu, Len_US
dc.contributor.authorMifsud, Wen_US
dc.contributor.authorApps, Jen_US
dc.contributor.authorThom, Men_US
dc.contributor.authorHubank, Men_US
dc.contributor.authorForshew, Ten_US
dc.contributor.authorCross, JHen_US
dc.contributor.authorHargrave, Den_US
dc.contributor.authorHam, Jen_US
dc.contributor.authorJacques, TSen_US
dc.coverage.spatialGermanyen_US
dc.date.accessioned2017-12-19T10:42:38Z
dc.date.issued2018-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/29058119en_US
dc.identifier10.1007/s00401-017-1773-zen_US
dc.identifier.citationActa Neuropathol, 2018, 135 (1), pp. 115 - 129en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/974
dc.identifier.eissn1432-0533en_US
dc.identifier.doi10.1007/s00401-017-1773-zen_US
dc.description.abstractGlioneuronal tumours are an important cause of treatment-resistant epilepsy. Subtypes of tumour are often poorly discriminated by histological features and may be difficult to diagnose due to a lack of robust diagnostic tools. This is illustrated by marked variability in the reported frequencies across different epilepsy surgical series. To address this, we used DNA methylation arrays and RNA sequencing to assay the methylation and expression profiles within a large cohort of glioneuronal tumours. By adopting a class discovery approach, we were able to identify two distinct groups of glioneuronal tumour, which only partially corresponded to the existing histological classification. Furthermore, by additional molecular analyses, we were able to identify pathogenic mutations in BRAF and FGFR1, specific to each group, in a high proportion of cases. Finally, by interrogating our expression data, we were able to show that each molecular group possessed expression phenotypes suggesting different cellular differentiation: astrocytic in one group and oligodendroglial in the second. Informed by this, we were able to identify CCND1, CSPG4, and PDGFRA as immunohistochemical targets which could distinguish between molecular groups. Our data suggest that the current histological classification of glioneuronal tumours does not adequately represent their underlying biology. Instead, we show that there are two molecular groups within glioneuronal tumours. The first of these displays astrocytic differentiation and is driven by BRAF mutations, while the second displays oligodendroglial differentiation and is driven by FGFR1 mutations.en_US
dc.format.extent115 - 129en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectDysembryoplastic neuroepithelial tumouren_US
dc.subjectEpilepsyen_US
dc.subjectGangliogliomaen_US
dc.subjectGlioneuronal tumouren_US
dc.subjectLEATen_US
dc.titleComprehensive molecular characterisation of epilepsy-associated glioneuronal tumours.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-10-03en_US
rioxxterms.versionofrecord10.1007/s00401-017-1773-zen_US
rioxxterms.licenseref.startdate2018-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfActa Neuropatholen_US
pubs.issue1en_US
pubs.notesNo embargoen_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/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublisheden_US
pubs.volume135en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamGlioma Teamen_US
icr.researchteamTranslational Genomicsen_US
dc.contributor.icrauthorHubank, Michaelen_US
dc.contributor.icrauthorMarsden,en_US
dc.contributor.icrauthorIzquierdo Delgado, Elisaen_US


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