dc.contributor.author | Burford, A | |
dc.contributor.author | Mackay, A | |
dc.contributor.author | Popov, S | |
dc.contributor.author | Vinci, M | |
dc.contributor.author | Carvalho, D | |
dc.contributor.author | Clarke, M | |
dc.contributor.author | Izquierdo, E | |
dc.contributor.author | Avery, A | |
dc.contributor.author | Jacques, TS | |
dc.contributor.author | Ingram, WJ | |
dc.contributor.author | Moore, AS | |
dc.contributor.author | Frawley, K | |
dc.contributor.author | Hassall, TE | |
dc.contributor.author | Robertson, T | |
dc.contributor.author | Jones, C | |
dc.date.accessioned | 2021-01-21T14:41:42Z | |
dc.date.issued | 2018-01-18 | |
dc.identifier.citation | Scientific reports, 2018, 8 (1), pp. 1032 - ? | |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4304 | |
dc.identifier.eissn | 2045-2322 | |
dc.identifier.doi | 10.1038/s41598-018-19389-9 | |
dc.description.abstract | Astroblastomas are rare brain tumours which predominate in children and young adults, and have a controversial claim as a distinct entity, with no established WHO grade. Reports suggest a better outcome than high grade gliomas, though they frequently recur. Recently, they have been described to overlap with a newly-discovered group of tumours described as'high grade neuroepithelial tumour with MN1 alteration' (CNS HGNET-MN1), defined by global methylation patterns and strongly associated with gene fusions targeting MN1. We have studied a unique case of astroblastoma arising in a 6 year-old girl, with multiple recurrences over a period of 10 years, with the pathognomonic MN1:BEND2 fusion. Exome sequencing allowed for a phylogenetic reconstruction of tumour evolution, which when integrated with clinical, pathological and radiological data provide for a detailed understanding of disease progression, with initial treatment driving tumour dissemination along four distinct trajectories. Infiltration of distant sites was associated with a later genome doubling, whilst there was evidence of convergent evolution of different lesions acquiring distinct alterations targeting NF-κB. These data represent an unusual opportunity to understand the evolutionary history of a highly recurrent childhood brain tumour, and provide novel therapeutic targets for astroblastoma/CNS HGNET-MN1. | |
dc.format | Electronic | |
dc.format.extent | 1032 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasms, Neuroepithelial | |
dc.subject | Translocation, Genetic | |
dc.subject | Recurrence | |
dc.subject | Trans-Activators | |
dc.subject | Oncogene Proteins, Fusion | |
dc.subject | Tumor Suppressor Proteins | |
dc.subject | Immunohistochemistry | |
dc.subject | In Situ Hybridization, Fluorescence | |
dc.subject | Age Factors | |
dc.subject | Child | |
dc.subject | Female | |
dc.subject | Neoplasm Grading | |
dc.subject | Whole Exome Sequencing | |
dc.title | The ten-year evolutionary trajectory of a highly recurrent paediatric high grade neuroepithelial tumour with MN1:BEND2 fusion. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2017-12-29 | |
rioxxterms.versionofrecord | 10.1038/s41598-018-19389-9 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-01-18 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Scientific reports | |
pubs.issue | 1 | |
pubs.notes | Not known | |
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 | |
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.publication-status | Published | |
pubs.volume | 8 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Glioma Team | |
dc.contributor.icrauthor | Mackay, Alan | |
dc.contributor.icrauthor | Jones, Chris | |