PT  - JOURNAL ARTICLE
AU  - Clarke, Matthew
AU  - Mackay, Alan
AU  - Ismer, Britta
AU  - Pickles, Jessica C.
AU  - Tatevossian, Ruth G.
AU  - Newman, Scott
AU  - Bale, Tejus A.
AU  - Stoler, Iris
AU  - Izquierdo, Elisa
AU  - Temelso, Sara
AU  - Carvalho, Diana M.
AU  - Molinari, Valeria
AU  - Burford, Anna
AU  - Howell, Louise
AU  - Virasami, Alex
AU  - Fairchild, Amy R.
AU  - Avery, Aimee
AU  - Chalker, Jane
AU  - Kristiansen, Mark
AU  - Haupfear, Kelly
AU  - Dalton, James D.
AU  - Orisme, Wilda
AU  - Wen, Ji
AU  - Hubank, Michael
AU  - Kurian, Kathreena M.
AU  - Rowe, Catherine
AU  - Maybury, Mellissa
AU  - Crosier, Stephen
AU  - Knipstein, Jeffrey
AU  - Schüller, Ulrich
AU  - Kordes, Uwe
AU  - Kram, David E.
AU  - Snuderl, Matija
AU  - Bridges, Leslie
AU  - Martin, Andrew J.
AU  - Doey, Lawrence J.
AU  - Al-Sarraj, Safa
AU  - Chandler, Christopher
AU  - Zebian, Bassel
AU  - Cairns, Claire
AU  - Natrajan, Rachael
AU  - Boult, Jessica K.R.
AU  - Robinson, Simon P.
AU  - Sill, Martin
AU  - Dunkel, Ira J.
AU  - Gilheeney, Stephen W.
AU  - Rosenblum, Marc K.
AU  - Hughes, Debbie
AU  - Proszek, Paula Z.
AU  - Macdonald, Tobey J.
AU  - Preusser, Matthias
AU  - Haberler, Christine
AU  - Slavc, Irene
AU  - Packer, Roger
AU  - Ng, Ho-Keung
AU  - Caspi, Shani
AU  - Popović, Mara
AU  - Faganel Kotnik, Barbara
AU  - Wood, Matthew D.
AU  - Baird, Lissa
AU  - Davare, Monika Ashok
AU  - Solomon, David A.
AU  - Olsen, Thale Kristin
AU  - Brandal, Petter
AU  - Farrell, Michael
AU  - Cryan, Jane B.
AU  - Capra, Michael
AU  - Karremann, Michael
AU  - Schittenhelm, Jens
AU  - Schuhmann, Martin U.
AU  - Ebinger, Martin
AU  - Dinjens, Winand N.M.
AU  - Kerl, Kornelius
AU  - Hettmer, Simone
AU  - Pietsch, Torsten
AU  - Andreiuolo, Felipe
AU  - Driever, Pablo Hernáiz
AU  - Korshunov, Andrey
AU  - Hiddingh, Lotte
AU  - Worst, Barbara C.
AU  - Sturm, Dominik
AU  - Zuckermann, Marc
AU  - Witt, Olaf
AU  - Bloom, Tabitha
AU  - Mitchell, Clare
AU  - Miele, Evelina
AU  - Colafati, Giovanna Stefania
AU  - Diomedi-Camassei, Francesca
AU  - Bailey, Simon
AU  - Moore, Andrew S.
AU  - Hassall, Timothy E.G.
AU  - Lowis, Stephen P.
AU  - Tsoli, Maria
AU  - Cowley, Mark J.
AU  - Ziegler, David S.
AU  - Karajannis, Matthias A.
AU  - Aquilina, Kristian
AU  - Hargrave, Darren R.
AU  - Carceller, Fernando
AU  - Marshall, Lynley V.
AU  - von Deimling, Andreas
AU  - Kramm, Christof M.
AU  - Pfister, Stefan M.
AU  - Sahm, Felix
AU  - Baker, Suzanne J.
AU  - Mastronuzzi, Angela
AU  - Carai, Andrea
AU  - Vinci, Maria
AU  - Capper, David
AU  - Popov, Sergey
AU  - Ellison, David W.
AU  - Jacques, Thomas S.
AU  - Jones, David T.W.
AU  - Jones, Chris
TI  - Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes
AID  - 10.1158/2159-8290.CD-19-1030
DP  - 2020 Jul 01
TA  - Cancer Discovery
PG  - 942--963
VI  - 10
IP  - 7
4099  - http://cancerdiscovery.aacrjournals.org/content/10/7/942.short
4100  - http://cancerdiscovery.aacrjournals.org/content/10/7/942.full
SO  - Cancer Discov2020 Jul 01; 10
AB  - 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 video: https://vimeo.com/438254885See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890