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dc.contributor.authorPiccirillo, SGM
dc.contributor.authorColman, S
dc.contributor.authorPotter, NE
dc.contributor.authorvan Delft, FW
dc.contributor.authorLillis, S
dc.contributor.authorCarnicer, M-J
dc.contributor.authorKearney, L
dc.contributor.authorWatts, C
dc.contributor.authorGreaves, M
dc.date.accessioned2020-08-05T13:56:34Z
dc.date.issued2015-01-13
dc.identifier.citationStem cell reports, 2015, 4 (1), pp. 7 - 15
dc.identifier.issn2213-6711
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3908
dc.identifier.eissn2213-6711
dc.identifier.doi10.1016/j.stemcr.2014.11.003
dc.description.abstractGlioblastoma (GBM) is a lethal malignancy whose clinical intransigence has been linked to extensive intraclonal genetic and phenotypic diversity and the common emergence of therapeutic resistance. This interpretation embodies the implicit assumption that cancer stem cells or tumor-propagating cells are themselves genetically and functionally diverse. To test this, we screened primary GBM tumors by SNP array to identify copy number alterations (a minimum of three) that could be visualized in single cells by multicolor fluorescence in situ hybridization. Interrogation of neurosphere-derived cells (from four patients) and cells derived from secondary transplants of these same cells in NOD-SCID mice allowed us to infer the clonal and phylogenetic architectures. Whole-exome sequencing and single-cell genetic analysis in one case revealed a more complex clonal structure. This proof-of-principle experiment revealed that subclones in each GBM had variable regenerative or stem cell activity, and highlighted genetic alterations associated with more competitive propagating activity in vivo.
dc.formatPrint-Electronic
dc.format.extent7 - 15
dc.languageeng
dc.language.isoeng
dc.publisherCELL PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectGlioblastoma
dc.subjectBrain Neoplasms
dc.subjectDisease Progression
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectGenomics
dc.subjectPhenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectNeoplastic Stem Cells
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.subjectDNA Copy Number Variations
dc.subjectSingle-Cell Analysis
dc.subjectHigh-Throughput Nucleotide Sequencing
dc.subjectHeterografts
dc.titleGenetic and functional diversity of propagating cells in glioblastoma.
dc.typeJournal Article
dcterms.dateAccepted2014-11-18
rioxxterms.versionofrecord10.1016/j.stemcr.2014.11.003
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2015-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfStem cell reports
pubs.issue1
pubs.notesNot 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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Biology of Childhood Leukaemia
pubs.publication-statusPublished
pubs.volume4
pubs.embargo.termsNot known
icr.researchteamBiology of Childhood Leukaemia
dc.contributor.icrauthorGreaves, Melvyn


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