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dc.contributor.authorStone, TJ
dc.contributor.authorKeeley, A
dc.contributor.authorVirasami, A
dc.contributor.authorHarkness, W
dc.contributor.authorTisdall, M
dc.contributor.authorIzquierdo Delgado, E
dc.contributor.authorGutteridge, A
dc.contributor.authorBrooks, T
dc.contributor.authorKristiansen, M
dc.contributor.authorChalker, J
dc.contributor.authorWilkhu, L
dc.contributor.authorMifsud, W
dc.contributor.authorApps, J
dc.contributor.authorThom, M
dc.contributor.authorHubank, M
dc.contributor.authorForshew, T
dc.contributor.authorCross, JH
dc.contributor.authorHargrave, D
dc.contributor.authorHam, J
dc.contributor.authorJacques, TS
dc.date.accessioned2017-12-19T10:42:38Z
dc.date.issued2018-01-01
dc.identifier.citationActa neuropathologica, 2018, 135 (1), pp. 115 - 129
dc.identifier.issn0001-6322
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/974
dc.identifier.eissn1432-0533
dc.identifier.doi10.1007/s00401-017-1773-z
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.
dc.formatPrint-Electronic
dc.format.extent115 - 129
dc.languageeng
dc.language.isoeng
dc.publisherSPRINGER
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectNeoplasms, Neuroepithelial
dc.subjectGanglioglioma
dc.subjectBrain Neoplasms
dc.subjectEpilepsy
dc.subjectProto-Oncogene Proteins B-raf
dc.subjectCohort Studies
dc.subjectDNA Methylation
dc.subjectGene Expression
dc.subjectPhenotype
dc.subjectMutation
dc.subjectAdolescent
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectFemale
dc.subjectMale
dc.subjectReceptor, Fibroblast Growth Factor, Type 1
dc.titleComprehensive molecular characterisation of epilepsy-associated glioneuronal tumours.
dc.typeJournal Article
dcterms.dateAccepted2017-10-03
rioxxterms.versionofrecord10.1007/s00401-017-1773-z
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfActa neuropathologica
pubs.issue1
pubs.notesNo embargo
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.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-statusPublished
pubs.volume135
pubs.embargo.termsNo embargo
icr.researchteamGlioma Team
icr.researchteamTranslational Genomics
dc.contributor.icrauthorIzquierdo Delgado, Elisa


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