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Nicolas De Jay, Gustavo Turecki, Florence M.G. Cavalli, Yixing Hu, Alexis Blanchet-Cohen, Corina Nagy, W. Todd Farmer, Andréa Allaire, Hervé Sartelet, Louis Crevier, Roy W. R. Dudley, Jiannis Ragoussis, Marie Coutelier, Maxime Richer, Maria C. Vladoiu, Livia Garzia, Michael D. Taylor, Claudia L. Kleinman, Valerie Larouche, Jean Monlong, Jeffrey Atkinson, Nada Jabado, Guillaume Bourque, Laura K. Donovan, Keith K. Murai, Benjamin Ellezam, Pierre-Eric Lutz, Jean-Pierre Farmer, Brice Poreau, Leonie G. Mikael, Alexander G. Weil, Mariella G. Filbin, Steven Hébert, Selin Jessa, Santiago Costantino, Steffen Albrecht, Damien Faury, Peter B. Dirks, Brian Krug, Melissa K. McConechy, McGill University = Université McGill [Montréal, Canada], Lady Davis Institute for Medical Research [Montréal], McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, The Hospital for sick children [Toronto] (SickKids), McGill University Health Center [Montreal] (MUHC), Centre Hospitalier Universitaire [Grenoble] (CHU), Santa Cruz Genomics Institute, University of California [Santa Cruz] (UCSC), University of California-University of California, Zebralog GmbH & Co. KG, Institut des Neurosciences Cellulaires et Intégratives (INCI), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry [Montréal], Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montreal General Hospital, McGill University and Genome Quebec Innovation Centre, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], This work was supported by funding from: a Large-Scale Applied Research Project grant from Genome Quebec, Genome Canada, the Government of Canada and the Ministère de l'Économie, de la Science et de l’Innovation du Québec, with the support of the Ontario Research Fund through funding provided by the Government of Ontario to N.J., M.D.T., C.L.K., P.B.D., G.B., J.R. and L.G., the Canadian Institutes for Health Research (CIHR grant nos. PJT-156086, to C.L.K., and MOP-286756 and FDN-154307, to N.J.), the US National Institutes of Health (NIH grant nos. P01-CA196539, to N.J., R01CA148699 and R01CA159859, to M.D.T.), the Canadian Cancer Society (CCSRI grant no. 705182), NSERC (grant no. RGPIN-2016-04911) and the Fonds de Recherche du Québec en Santé (FRQS) salary award to C.L.K., National Sciences and Engineering Research Council (grant no. NSERC-448167-2013) and FRQS (grant no. 25348) to G.B., CFI Leaders Opportunity Fund (grant nos. 32557, to J.R., and 33902, to C.L.K.), Genome Canada Science Technology Innovation Centre, Compute Canada Resource Allocation Project (grant no. WST-164-AB) and Genome Canada Genome Innovation Node (grant no. 244819) to J.R., and and the Fondation Charles-Bruneau. Data analyses were enabled by computer and storage resources provided by Compute Canada and Calcul Québec. N.J. is a member of the Penny Cole Laboratory and the recipient of a Chercheur Boursier, Chaire de Recherche Award from the FRQS. This work was performed within the context of the International Childhood Astrocytoma Integrated Genomic and Epigenomic (ICHANGE) consortium, and the Stand Up to Cancer (SU2C) Canada Cancer Stem Cell Dream Team Research Funding (grant no. SU2C-AACR-DT-19-15, to M.D.T. and N.J.) and SU2C St. Baldrick’s Pediatric Dream Team Translational Research Grant (no. SU2C-AACR-DT1113, to M.D.T.), with funding from Genome Canada and Genome Quebec. Stand Up to Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. M.D.T. is supported by The Pediatric Brain Tumour Foundation, The Canadian Institutes of Health Research, The Cure Search Foundation, b.r.a.i.n.child, Meagan’s Walk, SWIFTY Foundation, Genome Canada, Genome BC, Genome Quebec, the Ontario Research Fund, Worldwide Cancer Research, V-Foundation for Cancer Research, Cancer Research UK Brain Tumour Award, Canadian Cancer Society Research Institute Impact grant and the Garron Family Chair in Childhood Cancer Research at the Hospital for Sick Children and the University of Toronto. S.J. is supported by a fellowship from CIHR. A.B.-C. is supported by a fellowship from FRQS and TD/LDI. N.D.J. is a recipient of a fellowship from FRQS and RMGA. M.K.M. is funded by a CIHR Banting postdoctoral fellowship. We thank K. Mann, S. Spira and J. Di Noia for critical reading of the manuscript, and S. Krumholtz for graphical editing of figures. We are especially grateful for the generous philanthropic donations of the Fondation Charles-Bruneau, and the Kat D-DIPG, Poppies for Irina and We Love You Connie Foundations.