Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas
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Published:2019-09-25
Issue:1
Volume:10
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Guerreiro Stucklin Ana S.ORCID, Ryall Scott, Fukuoka Kohei, Zapotocky Michal, Lassaletta Alvaro, Li Christopher, Bridge Taylor, Kim Byungjin, Arnoldo Anthony, Kowalski Paul E., Zhong Yvonne, Johnson Monique, Li ClaireORCID, Ramani Arun K., Siddaway Robert, Nobre Liana Figueiredo, de Antonellis Pasqualino, Dunham Christopher, Cheng Sylvia, Boué Daniel R., Finlay Jonathan L., Coven Scott L., de Prada Inmaculada, Perez-Somarriba Marta, Faria Claudia C., Grotzer Michael A., Rushing Elisabeth, Sumerauer David, Zamecnik Josef, Krskova Lenka, Garcia Ariza Miguel, Cruz Ofelia, Morales La Madrid Andres, Solano Palma, Terashima Keita, Nakano YoshikoORCID, Ichimura KoichiORCID, Nagane MotooORCID, Sakamoto Hiroaki, Gil-da-Costa Maria Joao, Silva Roberto, Johnston Donna L., Michaud Jean, Wilson Bev, van Landeghem Frank K. H., Oviedo Angelica, McNeely P. Daniel, Crooks Bruce, Fried Iris, Zhukova Nataliya, Hansford Jordan R.ORCID, Nageswararao Amulya, Garzia Livia, Shago Mary, Brudno Michael, Irwin Meredith S., Bartels Ute, Ramaswamy VijayORCID, Bouffet Eric, Taylor Michael D., Tabori Uri, Hawkins Cynthia
Abstract
AbstractInfant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinasesALK,ROS1,NTRKandMET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harborRAS/MAPKpathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.
Funder
Canadian Cancer Society Research Institute Gouvernement du Canada | Canadian Institutes of Health Research A Kids’ Brain Tumor Cure Foundation, aka The PLGA foundation RESTRACOMP of the Hospital for Sick Children Ontario Graduate Scholarship RESTRACOMP of the Hospital for Sick Children Garron Family Cancer Center
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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