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dc.contributor.authorClarke, Men_US
dc.contributor.authorMackay, Aen_US
dc.contributor.authorIsmer, Ben_US
dc.contributor.authorPickles, JCen_US
dc.contributor.authorTatevossian, RGen_US
dc.contributor.authorNewman, Sen_US
dc.contributor.authorBale, TAen_US
dc.contributor.authorStoler, Ien_US
dc.contributor.authorIzquierdo, Een_US
dc.contributor.authorTemelso, Sen_US
dc.contributor.authorCarvalho, DMen_US
dc.contributor.authorMolinari, Ven_US
dc.contributor.authorBurford, Aen_US
dc.contributor.authorHowell, Len_US
dc.contributor.authorVirasami, Aen_US
dc.contributor.authorFairchild, ARen_US
dc.contributor.authorAvery, Aen_US
dc.contributor.authorChalker, Jen_US
dc.contributor.authorKristiansen, Men_US
dc.contributor.authorHaupfear, Ken_US
dc.contributor.authorDalton, JDen_US
dc.contributor.authorOrisme, Wen_US
dc.contributor.authorWen, Jen_US
dc.contributor.authorHubank, Men_US
dc.contributor.authorKurian, KMen_US
dc.contributor.authorRowe, Cen_US
dc.contributor.authorMaybury, Men_US
dc.contributor.authorCrosier, Sen_US
dc.contributor.authorKnipstein, Jen_US
dc.contributor.authorSchüller, Uen_US
dc.contributor.authorKordes, Uen_US
dc.contributor.authorKram, DEen_US
dc.contributor.authorSnuderl, Men_US
dc.contributor.authorBridges, Len_US
dc.contributor.authorMartin, AJen_US
dc.contributor.authorDoey, LJen_US
dc.contributor.authorAl-Sarraj, Sen_US
dc.contributor.authorChandler, Cen_US
dc.contributor.authorZebian, Ben_US
dc.contributor.authorCairns, Cen_US
dc.contributor.authorNatrajan, Ren_US
dc.contributor.authorBoult, JKRen_US
dc.contributor.authorRobinson, SPen_US
dc.contributor.authorSill, Men_US
dc.contributor.authorDunkel, IJen_US
dc.contributor.authorGilheeney, SWen_US
dc.contributor.authorRosenblum, MKen_US
dc.contributor.authorHughes, Den_US
dc.contributor.authorProszek, PZen_US
dc.contributor.authorMacdonald, TJen_US
dc.contributor.authorPreusser, Men_US
dc.contributor.authorHaberler, Cen_US
dc.contributor.authorSlavc, Ien_US
dc.contributor.authorPacker, Ren_US
dc.contributor.authorNg, H-Ken_US
dc.contributor.authorCaspi, Sen_US
dc.contributor.authorPopović, Men_US
dc.contributor.authorFaganel Kotnik, Ben_US
dc.contributor.authorWood, MDen_US
dc.contributor.authorBaird, Len_US
dc.contributor.authorDavare, MAen_US
dc.contributor.authorSolomon, DAen_US
dc.contributor.authorOlsen, TKen_US
dc.contributor.authorBrandal, Pen_US
dc.contributor.authorFarrell, Men_US
dc.contributor.authorCryan, JBen_US
dc.contributor.authorCapra, Men_US
dc.contributor.authorKarremann, Men_US
dc.contributor.authorSchittenhelm, Jen_US
dc.contributor.authorSchuhmann, MUen_US
dc.contributor.authorEbinger, Men_US
dc.contributor.authorDinjens, WNMen_US
dc.contributor.authorKerl, Ken_US
dc.contributor.authorHettmer, Sen_US
dc.contributor.authorPietsch, Ten_US
dc.contributor.authorAndreiuolo, Fen_US
dc.contributor.authorDriever, PHen_US
dc.contributor.authorKorshunov, Aen_US
dc.contributor.authorHiddingh, Len_US
dc.contributor.authorWorst, BCen_US
dc.contributor.authorSturm, Den_US
dc.contributor.authorZuckermann, Men_US
dc.contributor.authorWitt, Oen_US
dc.contributor.authorBloom, Ten_US
dc.contributor.authorMitchell, Cen_US
dc.contributor.authorMiele, Een_US
dc.contributor.authorColafati, GSen_US
dc.contributor.authorDiomedi-Camassei, Fen_US
dc.contributor.authorBailey, Sen_US
dc.contributor.authorMoore, ASen_US
dc.contributor.authorHassall, TEGen_US
dc.contributor.authorLowis, SPen_US
dc.contributor.authorTsoli, Men_US
dc.contributor.authorCowley, MJen_US
dc.contributor.authorZiegler, DSen_US
dc.contributor.authorKarajannis, MAen_US
dc.contributor.authorAquilina, Ken_US
dc.contributor.authorHargrave, DRen_US
dc.contributor.authorCarceller, Fen_US
dc.contributor.authorMarshall, LVen_US
dc.contributor.authorvon Deimling, Aen_US
dc.contributor.authorKramm, CMen_US
dc.contributor.authorPfister, SMen_US
dc.contributor.authorSahm, Fen_US
dc.contributor.authorBaker, SJen_US
dc.contributor.authorMastronuzzi, Aen_US
dc.contributor.authorCarai, Aen_US
dc.contributor.authorVinci, Men_US
dc.contributor.authorCapper, Den_US
dc.contributor.authorPopov, Sen_US
dc.contributor.authorEllison, DWen_US
dc.contributor.authorJacques, TSen_US
dc.contributor.authorJones, DTWen_US
dc.contributor.authorJones, Cen_US
dc.date.accessioned2020-03-31T12:29:06Z
dc.date.issued2020-07
dc.identifier.citationCancer discovery, 2020, 10 (7), pp. 942 - 963
dc.identifier.issn2159-8274
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3555
dc.identifier.eissn2159-8290
dc.identifier.doi10.1158/2159-8290.cd-19-1030
dc.description.abstractInfant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting <i>ALK</i> (<i>n</i> = 31), <i>NTRK1/2/3</i> (<i>n</i> = 21), <i>ROS1</i> (<i>n</i> = 9), and <i>MET</i> (<i>n</i> = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of <i>ALK, NTRK1/2/3, ROS1</i>, or <i>MET</i> gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.<i>See related commentary by Szulzewsky and Cimino, p. 904</i>.<i>This article is highlighted in the In This Issue feature, p. 890</i>.en_US
dc.formatPrint-Electronic
dc.format.extent942 - 963
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleInfant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.
dc.typeJournal Article
dcterms.dateAccepted2020-03-20
rioxxterms.versionofrecord10.1158/2159-8290.cd-19-1030
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-07
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer discoveryen_US
pubs.issue7
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/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genomics
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/Functional Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Glioma Team
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.)
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.publication-statusPublished
pubs.volume10en_US
pubs.embargo.termsNot known
icr.researchteamFunctional Genomicsen_US
icr.researchteamGlioma Teamen_US
icr.researchteamTranslational Genomicsen_US
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorJones, Chrisen
dc.contributor.icrauthorMackay, Alanen
dc.contributor.icrauthorNatrajan, Rachaelen
dc.contributor.icrauthorBoult, Jessicaen
dc.contributor.icrauthorRobinson, Simonen
dc.contributor.icrauthorHubank, Michaelen


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