dc.contributor.author | International Cancer Genome Consortium PedBrain Tumor Project, | |
dc.date.accessioned | 2017-01-04T16:26:58Z | |
dc.date.issued | 2016-11-01 | |
dc.identifier.citation | Nature medicine, 2016, 22 (11), pp. 1314 - 1320 | |
dc.identifier.issn | 1078-8956 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/370 | |
dc.identifier.eissn | 1546-170X | |
dc.identifier.doi | 10.1038/nm.4204 | |
dc.description.abstract | Pediatric glioblastoma is one of the most common and most deadly brain tumors in childhood. Using an integrative genetic analysis of 53 pediatric glioblastomas and five in vitro model systems, we identified previously unidentified gene fusions involving the MET oncogene in ∼10% of cases. These MET fusions activated mitogen-activated protein kinase (MAPK) signaling and, in cooperation with lesions compromising cell cycle regulation, induced aggressive glial tumors in vivo. MET inhibitors suppressed MET tumor growth in xenograft models. Finally, we treated a pediatric patient bearing a MET-fusion-expressing glioblastoma with the targeted inhibitor crizotinib. This therapy led to substantial tumor shrinkage and associated relief of symptoms, but new treatment-resistant lesions appeared, indicating that combination therapies are likely necessary to achieve a durable clinical response. | |
dc.format | Print-Electronic | |
dc.format.extent | 1314 - 1320 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.subject | International Cancer Genome Consortium PedBrain Tumor Project | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Mice, SCID | |
dc.subject | Glioblastoma | |
dc.subject | Brain Neoplasms | |
dc.subject | Anilides | |
dc.subject | Pyrazoles | |
dc.subject | Pyridines | |
dc.subject | Quinolines | |
dc.subject | Mitogen-Activated Protein Kinases | |
dc.subject | Proteins | |
dc.subject | Microtubule-Associated Proteins | |
dc.subject | Oncogene Proteins, Fusion | |
dc.subject | DNA, Neoplasm | |
dc.subject | RNA, Messenger | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Sequence Analysis, DNA | |
dc.subject | Signal Transduction | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Child | |
dc.subject | Child, Preschool | |
dc.subject | Infant | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Proto-Oncogene Proteins c-met | |
dc.subject | Receptor-Like Protein Tyrosine Phosphatases, Class 5 | |
dc.subject | Young Adult | |
dc.subject | Crizotinib | |
dc.title | Recurrent MET fusion genes represent a drug target in pediatric glioblastoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-09-15 | |
rioxxterms.versionofrecord | 10.1038/nm.4204 | |
rioxxterms.licenseref.startdate | 2016-11 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature medicine | |
pubs.issue | 11 | |
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 | 22 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Glioma Team | |
dc.contributor.icrauthor | Jones, Chris | |
dc.contributor.icrauthor | Bjerke, Lynn | |