RT Journal Article
SR Electronic
T1 Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes
JF Cancer Discovery
JO Cancer Discov
FD American Association for Cancer Research
SP 942
OP 963
DO 10.1158/2159-8290.CD-19-1030
VO 10
IS 7
A1 Clarke, Matthew
A1 Mackay, Alan
A1 Ismer, Britta
A1 Pickles, Jessica C.
A1 Tatevossian, Ruth G.
A1 Newman, Scott
A1 Bale, Tejus A.
A1 Stoler, Iris
A1 Izquierdo, Elisa
A1 Temelso, Sara
A1 Carvalho, Diana M.
A1 Molinari, Valeria
A1 Burford, Anna
A1 Howell, Louise
A1 Virasami, Alex
A1 Fairchild, Amy R.
A1 Avery, Aimee
A1 Chalker, Jane
A1 Kristiansen, Mark
A1 Haupfear, Kelly
A1 Dalton, James D.
A1 Orisme, Wilda
A1 Wen, Ji
A1 Hubank, Michael
A1 Kurian, Kathreena M.
A1 Rowe, Catherine
A1 Maybury, Mellissa
A1 Crosier, Stephen
A1 Knipstein, Jeffrey
A1 Schüller, Ulrich
A1 Kordes, Uwe
A1 Kram, David E.
A1 Snuderl, Matija
A1 Bridges, Leslie
A1 Martin, Andrew J.
A1 Doey, Lawrence J.
A1 Al-Sarraj, Safa
A1 Chandler, Christopher
A1 Zebian, Bassel
A1 Cairns, Claire
A1 Natrajan, Rachael
A1 Boult, Jessica K.R.
A1 Robinson, Simon P.
A1 Sill, Martin
A1 Dunkel, Ira J.
A1 Gilheeney, Stephen W.
A1 Rosenblum, Marc K.
A1 Hughes, Debbie
A1 Proszek, Paula Z.
A1 Macdonald, Tobey J.
A1 Preusser, Matthias
A1 Haberler, Christine
A1 Slavc, Irene
A1 Packer, Roger
A1 Ng, Ho-Keung
A1 Caspi, Shani
A1 Popović, Mara
A1 Faganel Kotnik, Barbara
A1 Wood, Matthew D.
A1 Baird, Lissa
A1 Davare, Monika Ashok
A1 Solomon, David A.
A1 Olsen, Thale Kristin
A1 Brandal, Petter
A1 Farrell, Michael
A1 Cryan, Jane B.
A1 Capra, Michael
A1 Karremann, Michael
A1 Schittenhelm, Jens
A1 Schuhmann, Martin U.
A1 Ebinger, Martin
A1 Dinjens, Winand N.M.
A1 Kerl, Kornelius
A1 Hettmer, Simone
A1 Pietsch, Torsten
A1 Andreiuolo, Felipe
A1 Driever, Pablo Hernáiz
A1 Korshunov, Andrey
A1 Hiddingh, Lotte
A1 Worst, Barbara C.
A1 Sturm, Dominik
A1 Zuckermann, Marc
A1 Witt, Olaf
A1 Bloom, Tabitha
A1 Mitchell, Clare
A1 Miele, Evelina
A1 Colafati, Giovanna Stefania
A1 Diomedi-Camassei, Francesca
A1 Bailey, Simon
A1 Moore, Andrew S.
A1 Hassall, Timothy E.G.
A1 Lowis, Stephen P.
A1 Tsoli, Maria
A1 Cowley, Mark J.
A1 Ziegler, David S.
A1 Karajannis, Matthias A.
A1 Aquilina, Kristian
A1 Hargrave, Darren R.
A1 Carceller, Fernando
A1 Marshall, Lynley V.
A1 von Deimling, Andreas
A1 Kramm, Christof M.
A1 Pfister, Stefan M.
A1 Sahm, Felix
A1 Baker, Suzanne J.
A1 Mastronuzzi, Angela
A1 Carai, Andrea
A1 Vinci, Maria
A1 Capper, David
A1 Popov, Sergey
A1 Ellison, David W.
A1 Jacques, Thomas S.
A1 Jones, David T.W.
A1 Jones, Chris
YR 2020
UL http://cancerdiscovery.aacrjournals.org/content/10/7/942.abstract
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