dc.contributor.author | Clarke, M | |
dc.contributor.author | Mackay, A | |
dc.contributor.author | Ismer, B | |
dc.contributor.author | Pickles, JC | |
dc.contributor.author | Tatevossian, RG | |
dc.contributor.author | Newman, S | |
dc.contributor.author | Bale, TA | |
dc.contributor.author | Stoler, I | |
dc.contributor.author | Izquierdo, E | |
dc.contributor.author | Temelso, S | |
dc.contributor.author | Carvalho, DM | |
dc.contributor.author | Molinari, V | |
dc.contributor.author | Burford, A | |
dc.contributor.author | Howell, L | |
dc.contributor.author | Virasami, A | |
dc.contributor.author | Fairchild, AR | |
dc.contributor.author | Avery, A | |
dc.contributor.author | Chalker, J | |
dc.contributor.author | Kristiansen, M | |
dc.contributor.author | Haupfear, K | |
dc.contributor.author | Dalton, JD | |
dc.contributor.author | Orisme, W | |
dc.contributor.author | Wen, J | |
dc.contributor.author | Hubank, M | |
dc.contributor.author | Kurian, KM | |
dc.contributor.author | Rowe, C | |
dc.contributor.author | Maybury, M | |
dc.contributor.author | Crosier, S | |
dc.contributor.author | Knipstein, J | |
dc.contributor.author | Schüller, U | |
dc.contributor.author | Kordes, U | |
dc.contributor.author | Kram, DE | |
dc.contributor.author | Snuderl, M | |
dc.contributor.author | Bridges, L | |
dc.contributor.author | Martin, AJ | |
dc.contributor.author | Doey, LJ | |
dc.contributor.author | Al-Sarraj, S | |
dc.contributor.author | Chandler, C | |
dc.contributor.author | Zebian, B | |
dc.contributor.author | Cairns, C | |
dc.contributor.author | Natrajan, R | |
dc.contributor.author | Boult, JKR | |
dc.contributor.author | Robinson, SP | |
dc.contributor.author | Sill, M | |
dc.contributor.author | Dunkel, IJ | |
dc.contributor.author | Gilheeney, SW | |
dc.contributor.author | Rosenblum, MK | |
dc.contributor.author | Hughes, D | |
dc.contributor.author | Proszek, PZ | |
dc.contributor.author | Macdonald, TJ | |
dc.contributor.author | Preusser, M | |
dc.contributor.author | Haberler, C | |
dc.contributor.author | Slavc, I | |
dc.contributor.author | Packer, R | |
dc.contributor.author | Ng, H-K | |
dc.contributor.author | Caspi, S | |
dc.contributor.author | Popović, M | |
dc.contributor.author | Faganel Kotnik, B | |
dc.contributor.author | Wood, MD | |
dc.contributor.author | Baird, L | |
dc.contributor.author | Davare, MA | |
dc.contributor.author | Solomon, DA | |
dc.contributor.author | Olsen, TK | |
dc.contributor.author | Brandal, P | |
dc.contributor.author | Farrell, M | |
dc.contributor.author | Cryan, JB | |
dc.contributor.author | Capra, M | |
dc.contributor.author | Karremann, M | |
dc.contributor.author | Schittenhelm, J | |
dc.contributor.author | Schuhmann, MU | |
dc.contributor.author | Ebinger, M | |
dc.contributor.author | Dinjens, WNM | |
dc.contributor.author | Kerl, K | |
dc.contributor.author | Hettmer, S | |
dc.contributor.author | Pietsch, T | |
dc.contributor.author | Andreiuolo, F | |
dc.contributor.author | Driever, PH | |
dc.contributor.author | Korshunov, A | |
dc.contributor.author | Hiddingh, L | |
dc.contributor.author | Worst, BC | |
dc.contributor.author | Sturm, D | |
dc.contributor.author | Zuckermann, M | |
dc.contributor.author | Witt, O | |
dc.contributor.author | Bloom, T | |
dc.contributor.author | Mitchell, C | |
dc.contributor.author | Miele, E | |
dc.contributor.author | Colafati, GS | |
dc.contributor.author | Diomedi-Camassei, F | |
dc.contributor.author | Bailey, S | |
dc.contributor.author | Moore, AS | |
dc.contributor.author | Hassall, TEG | |
dc.contributor.author | Lowis, SP | |
dc.contributor.author | Tsoli, M | |
dc.contributor.author | Cowley, MJ | |
dc.contributor.author | Ziegler, DS | |
dc.contributor.author | Karajannis, MA | |
dc.contributor.author | Aquilina, K | |
dc.contributor.author | Hargrave, DR | |
dc.contributor.author | Carceller, F | |
dc.contributor.author | Marshall, LV | |
dc.contributor.author | von Deimling, A | |
dc.contributor.author | Kramm, CM | |
dc.contributor.author | Pfister, SM | |
dc.contributor.author | Sahm, F | |
dc.contributor.author | Baker, SJ | |
dc.contributor.author | Mastronuzzi, A | |
dc.contributor.author | Carai, A | |
dc.contributor.author | Vinci, M | |
dc.contributor.author | Capper, D | |
dc.contributor.author | Popov, S | |
dc.contributor.author | Ellison, DW | |
dc.contributor.author | Jacques, TS | |
dc.contributor.author | Jones, DTW | |
dc.contributor.author | Jones, C | |
dc.date.accessioned | 2020-03-31T12:29:06Z | |
dc.date.issued | 2020-07-01 | |
dc.identifier.citation | Cancer discovery, 2020, 10 (7), pp. 942 - 963 | |
dc.identifier.issn | 2159-8274 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3555 | |
dc.identifier.eissn | 2159-8290 | |
dc.identifier.doi | 10.1158/2159-8290.cd-19-1030 | |
dc.description.abstract | Infant 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 ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 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 ALK, NTRK1/2/3, ROS1, or MET 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.See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890. | |
dc.format | Print-Electronic | |
dc.format.extent | 942 - 963 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-03-20 | |
rioxxterms.versionofrecord | 10.1158/2159-8290.cd-19-1030 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-07 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer discovery | |
pubs.issue | 7 | |
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/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-status | Published | |
pubs.volume | 10 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Functional Genomics | |
icr.researchteam | Glioma Team | |
icr.researchteam | Translational Genomics | |
icr.researchteam | Pre-Clinical MRI | |
dc.contributor.icrauthor | Clarke, Matthew | |
dc.contributor.icrauthor | Mackay, Alan | |
dc.contributor.icrauthor | Natrajan, Rachael | |
dc.contributor.icrauthor | Boult, Jessica | |
dc.contributor.icrauthor | Robinson, Simon | |
dc.contributor.icrauthor | Jones, Chris | |