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dc.contributor.authorBlandin, A-Fen_US
dc.contributor.authorDurand, Aen_US
dc.contributor.authorLitzler, Men_US
dc.contributor.authorTripp, Aen_US
dc.contributor.authorGuérin, Éen_US
dc.contributor.authorRuhland, Een_US
dc.contributor.authorObrecht, Aen_US
dc.contributor.authorKeime, Cen_US
dc.contributor.authorFuchs, Qen_US
dc.contributor.authorReita, Den_US
dc.contributor.authorLhermitte, Ben_US
dc.contributor.authorCoca, Aen_US
dc.contributor.authorJones, Cen_US
dc.contributor.authorRebel, ILen_US
dc.contributor.authorVilla, Pen_US
dc.contributor.authorNamer, IJen_US
dc.contributor.authorDontenwill, Men_US
dc.contributor.authorGuenot, Den_US
dc.contributor.authorEntz-Werle, Nen_US
dc.date.accessioned2020-05-28T11:24:02Z
dc.date.issued2019-11-26
dc.identifier.citationCancers, 2019, 11 (12)
dc.identifier.issn2072-6694
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3650
dc.identifier.eissn2072-6694
dc.identifier.doi10.3390/cancers11121875
dc.description.abstractBACKGROUND:Pediatric high-grade gliomas (pHGGs) are facing a very dismal prognosis and representative pre-clinical models are needed for new treatment strategies. Here, we examined the relevance of collecting functional, genomic, and metabolomics data to validate patient-derived models in a hypoxic microenvironment. METHODS:From our biobank of pediatric brain tumor-derived models, we selected 11 pHGGs driven by the histone H3.3K28M mutation. We compared the features of four patient tumors to their paired cell lines and mouse xenografts using NGS (next generation sequencing), aCGH (array comparative genomic hybridization), RNA sequencing, WES (whole exome sequencing), immunocytochemistry, and HRMAS (high resolution magic angle spinning) spectroscopy. We developed a multicellular in vitro model of cell migration to mimic the brain hypoxic microenvironment. The live cell technology Incucyte© was used to assess drug responsiveness in variable oxygen conditions. RESULTS:The concurrent 2D and 3D cultures generated from the same tumor sample exhibited divergent but complementary features, recreating the patient intra-tumor complexity. Genomic and metabolomic data described the metabolic changes during pHGG progression and supported hypoxia as an important key to preserve the tumor metabolism in vitro and cell dissemination present in patients. The neurosphere features preserved tumor development and sensitivity to treatment. CONCLUSION:We proposed a novel multistep work for the development and validation of patient-derived models, considering the immature and differentiated content and the tumor microenvironment of pHGGs.
dc.formatElectronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleHypoxic Environment and Paired Hierarchical 3D and 2D Models of Pediatric H3.3-Mutated Gliomas Recreate the Patient Tumor Complexity.
dc.typeJournal Article
dcterms.dateAccepted2019-11-15
rioxxterms.versionofrecord10.3390/cancers11121875
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-11-26
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancers
pubs.issue12
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
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-statusPublished
pubs.volume11
pubs.embargo.termsNot known
icr.researchteamSignalling & Cancer Metabolismen_US
icr.researchteamGlioma Teamen_US
dc.contributor.icrauthorTripp, Aurelienen
dc.contributor.icrauthorJones, Chrisen


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