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dc.contributor.authorSottoriva, Aen_US
dc.contributor.authorSpiteri, Ien_US
dc.contributor.authorPiccirillo, SGen_US
dc.contributor.authorTouloumis, Aen_US
dc.contributor.authorCollins, VPen_US
dc.contributor.authorMarioni, JCen_US
dc.contributor.authorCurtis, Cen_US
dc.contributor.authorWatts, Cen_US
dc.contributor.authorTavaré, Sen_US
dc.date.accessioned2018-11-19T12:02:03Z
dc.date.issued2013-03en_US
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2013, 110 (10), pp. 4009 - 4014en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2940
dc.identifier.eissn1091-6490en_US
dc.identifier.doi10.1073/pnas.1219747110en_US
dc.description.abstractGlioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure. However, the extent of intratumor heterogeneity as a result of tumor evolution is still poorly understood. To address this, we developed a unique surgical multisampling scheme to collect spatially distinct tumor fragments from 11 GB patients. We present an integrated genomic analysis that uncovers extensive intratumor heterogeneity, with most patients displaying different GB subtypes within the same tumor. Moreover, we reconstructed the phylogeny of the fragments for each patient, identifying copy number alterations in EGFR and CDKN2A/B/p14ARF as early events, and aberrations in PDGFRA and PTEN as later events during cancer progression. We also characterized the clonal organization of each tumor fragment at the single-molecule level, detecting multiple coexisting cell lineages. Our results reveal the genome-wide architecture of intratumor variability in GB across multiple spatial scales and patient-specific patterns of cancer evolution, with consequences for treatment design.en_US
dc.formatPrint-Electronicen_US
dc.format.extent4009 - 4014en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectHumansen_US
dc.subjectGlioblastomaen_US
dc.subjectBrain Neoplasmsen_US
dc.subjectChromosome Aberrationsen_US
dc.subjectDisease Progressionen_US
dc.subjectDNA, Neoplasmen_US
dc.subjectEvolution, Molecularen_US
dc.subjectPhylogenyen_US
dc.subjectBase Sequenceen_US
dc.subjectGenes, p16en_US
dc.subjectGenes, erbB-1en_US
dc.subjectDNA Copy Number Variationsen_US
dc.subjectTranscriptomeen_US
dc.titleIntratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1073/pnas.1219747110en_US
rioxxterms.licenseref.startdate2013-03en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfProceedings of the National Academy of Sciences of the United States of Americaen_US
pubs.issue10en_US
pubs.notes6 monthsen_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/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Evolutionary Genomics & Modelling
pubs.volume110en_US
pubs.embargo.terms6 monthsen_US
icr.researchteamEvolutionary Genomics & Modellingen_US
dc.contributor.icrauthorSottoriva, Andreaen_US
dc.contributor.icrauthorSpiteri Sagastume, Mariaen_US


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