ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2015
BRAF mutation and CDKN2A deletion define a clinically distinct subgroup of childhood secondary high-grade glioma.
Open access · bronzeAbstract read
In one paragraph
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
162citing papers in PubMed, 4 pooled it
17.3field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
162 citing papers in PubMed, 4 syntheses or guidelines pooled it, 283 citations in OpenAlex.
- The effects of dabrafenib and/or trametinib treatment in Braf V600-mutant glioma: a systematic review and meta-analysis.Neurosurgical review · 2024Pooled it
- Management of incidental brain tumors in children: a systematic review.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020Pooled it
- BRAF Mutation is Associated with an Improved Survival in Glioma-a Systematic Review and Meta-analysis.Molecular neurobiology · 2018Pooled it
- Association BetweenCancer control : journal of the Moffitt Cancer CenterPooled it
- Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in PediatricJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- BRAF Inhibition inJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- BRAF-amplified glioblastoma patients have a worse prognosis than those with BRAF mutation and are associated with amplification of MET, RHEB and CUL1.BMC neurology · 2026Article
- Co-targeting CDK4/6 and MEK reverses mesenchymal transition in therapy-refractory BRAF-altered pediatric high-grade glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Targeted therapies in adolescent and young adult patients with central nervous system tumors.Neuro-oncology advances · 2026Review
- From Diagnosis Delay to Targeted Therapy: A Retrospective Study of Pediatric DLGNT with a Comprehensive Literature Review.Cancers · 2026Article
- Integrated clinical and molecular landscape of disseminated pediatric low-grade glioma.Neuro-oncology · 2026Article
- From Molecular Alterations to the Targeted Therapy: Treatment of Thalamic Glioma in Pediatric Patients.International journal of molecular sciences · 2026Review
- Genomic analysis of PLNTY-like tumor progression into epithelioid glioblastoma: a case report.Acta neuropathologica communications · 2026Article
- Current Perspectives on Pediatric Low-Grade Gliomas: Focus on BRAF and MEK Inhibition.Brain tumor research and treatment · 2026Review
- Dabrafenib in pediatric patients withNeuro-oncology practice · 2025Article
- Radiology-based artificial intelligence for predicting targeted therapy response in pan-cancer: a comprehensive review.Journal of translational medicine · 2025Review
- Challenging CDKN2A assessment in BRAF-altered gliomas: lessons from a pleomorphic xanthoastrocytoma-enriched cohort.Acta neuropathologica communications · 2025Article
- Pediatric thalamic incidentalomas: a retrospective analysis of their characteristics, evolution, management, and prognostic factors for progression.Acta neurochirurgica · 2025Article
- Improving Global Access to Genomic Profiling in Rare Pediatric Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Myalgia and Rigidity as Adverse Effects of Trametinib Therapy.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
102 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors at 5 institutions in 3 countries.
Matthew MistryMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Nataliya ZhukovaMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Daniele MericoMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Patricia RakopoulosMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Rahul KrishnatryMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Mary ShagoMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
James StavropoulosMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Noa AlonMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Jason D PoleMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Peter N RayMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Vilma NavickieneMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Joshua MangerelMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Marc RemkeMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Pawel BuczkowiczMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Vijay RamaswamyMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Ana Guerreiro StucklinMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Martin LiMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Edwin J YoungMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Cindy ZhangMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Pedro Castelo-BrancoMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Doua BakryMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Suzanne LaughlinMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Adam ShlienMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Jennifer ChanMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Keith L LigonMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
James T RutkaMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Peter B DirksMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Michael D TaylorMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Mark GreenbergMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
David MalkinMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Annie HuangMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Eric BouffetMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Cynthia E HawkinsMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA.
Uri TaboriMatthew Mistry, Nataliya Zhukova, Daniele Merico, Rahul Krishnatry, Mary Shago, James Stavropoulos, Noa Alon, Peter N. Ray, Vilma Navickiene, Joshua Mangerel, Marc Remke, Vijay Ramaswamy, Ana Guerreiro Stucklin, Martin Li, Edwin J. Young, Cindy Zhang, Pedro Castelo-Branco, Doua Bakry, Suzanne Laughlin, James T. Rutka, Peter B. Dirks, Michael D. Taylor, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori; The Hospital for Sick Children; Matthew Mistry, Patricia Rakopoulos, Rahul Krishnatry, Joshua Mangerel, Pawel Buczkowicz, Ana Guerreiro Stucklin, Doua Bakry, Adam Shlien, Mark Greenberg, David Malkin, Annie Huang, Eric Bouffet, Cynthia E. Hawkins, and Uri Tabori, University of Toronto; Jason D. Pole, Pediatric Oncology Group of Ontario, Toronto, Ontario; Jennifer Chan, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada; Pedro Castelo-Branco, Universidade do Algarve, Faro, Portugal; Keith L. Ligon, Dana-Farber/Boston Children's Cancer Center, Boston, MA. uri.tabori@sickkids.ca.
University of Toronto · CADana-Farber Cancer Institute · USPediatric Oncology Group · CAUniversity of Algarve · PTUniversity of Calgary · CA
Funding
Therapeutic Opportunities for Pediatric AstrocytomaP01CA142536 · NCI · DANA-FARBER CANCER INST · PI SEGAL, ROSALIND A. · 2011 to 2015
$7.9MCanadian Institutes of Health Research MOP-123268NCI NIH HHS P01 CA142536NCI NIH HHS P01CA142536
Abstract
purposeTo uncover the genetic events leading to transformation of pediatric low-grade glioma (PLGG) to secondary high-grade glioma (sHGG). PATIENTS AND
methodsWe retrospectively identified patients with sHGG from a population-based cohort of 886 patients with PLGG with long clinical follow-up. Exome sequencing and array CGH were performed on available samples followed by detailed genetic analysis of the entire sHGG cohort. Clinical and outcome data of genetically distinct subgroups were obtained.
resultssHGG was observed in 2.9% of PLGGs (26 of 886 patients). Patients with sHGG had a high frequency of nonsilent somatic mutations compared with patients with primary pediatric high-grade glioma (HGG; median, 25 mutations per exome; P = .0042). Alterations in chromatin-modifying genes and telomere-maintenance pathways were commonly observed, whereas no sHGG harbored the BRAF-KIAA1549 fusion. The most recurrent alterations were BRAF V600E and CDKN2A deletion in 39% and 57% of sHGGs, respectively. Importantly, all BRAF V600E and 80% of CDKN2A alterations could be traced back to their PLGG counterparts. BRAF V600E distinguished sHGG from primary HGG (P = .0023), whereas BRAF and CDKN2A alterations were less commonly observed in PLGG that did not transform (P < .001 and P < .001 respectively). PLGGs with BRAF mutations had longer latency to transformation than wild-type PLGG (median, 6.65 years [range, 3.5 to 20.3 years] v 1.59 years [range, 0.32 to 15.9 years], respectively; P = .0389). Furthermore, 5-year overall survival was 75% ± 15% and 29% ± 12% for children with BRAF mutant and wild-type tumors, respectively (P = .024).
conclusionBRAF V600E mutations and CDKN2A deletions constitute a clinically distinct subtype of sHGG. The prolonged course to transformation for BRAF V600E PLGGs provides an opportunity for surgical interventions, surveillance, and targeted therapies to mitigate the outcome of sHGG.
Indexed as
Gene DeletionAdolescentBrain NeoplasmsCell Transformation, NeoplasticChildChild, PreschoolChromatinCyclin-Dependent Kinase Inhibitor p16Disease ProgressionFemaleFollow-Up StudiesGliomaHumansInfantMaleMutationBRAF protein, humanChromatinCyclin-Dependent Kinase Inhibitor p16Proto-Oncogene Proteins B-raf
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