Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

Ana S. Guerreiro Stucklin, Scott Ryall, Kohei Fukuoka, Michal Zapotocky, Alvaro Lassaletta, Christopher Li, Taylor Bridge, Byungjin Kim, Anthony Arnoldo, Paul E. Kowalski, Yvonne Zhong, Monique Johnson, Claire Li, Arun K. Ramani, Robert Siddaway, Liana Figueiredo Nobre, Pasqualino de Antonellis, Christopher Dunham, Sylvia Cheng, Daniel R. Boué, Jonathan L. Finlay, Scott L. Coven, Inmaculada de Prada, Marta Perez-Somarriba, Claudia C. Faria, Michael A. Grotzer, Elisabeth Rushing, David Sumerauer, Josef Zamecnik, Lenka Krskova, Miguel Garcia Ariza, Ofelia Cruz, Andres Morales La Madrid, Palma Solano, Keita Terashima, Yoshiko Nakano, Koichi Ichimura, Motoo Nagane, Hiroaki Sakamoto, Maria Joao Gil-da-Costa, Roberto Silva, Donna L. Johnston, Jean Michaud, Bev Wilson, Frank K. H. van Landeghem, Angelica Oviedo, P. Daniel McNeely, Bruce Crooks, Iris Fried, Nataliya Zhukova, Jordan R. Hansford, Amulya Nageswararao, Livia Garzia, Mary Shago, Michael Brudno, Meredith S. Irwin, Ute Bartels, Vijay Ramaswamy, Eric Bouffet, Michael D. Taylor, Uri Tabori and Cynthia Hawkins ()
Additional contact information
Ana S. Guerreiro Stucklin: The Hospital for Sick Children
Scott Ryall: The Hospital for Sick Children
Kohei Fukuoka: The Hospital for Sick Children
Michal Zapotocky: The Hospital for Sick Children
Alvaro Lassaletta: The Hospital for Sick Children
Christopher Li: The Hospital for Sick Children
Taylor Bridge: The Hospital for Sick Children
Byungjin Kim: The Hospital for Sick Children
Anthony Arnoldo: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children
Paul E. Kowalski: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children
Yvonne Zhong: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children
Monique Johnson: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children
Claire Li: Department of Pediatric Laboratory Medicine, The Hospital for Sick Children
Arun K. Ramani: The Hospital for Sick Children
Robert Siddaway: The Hospital for Sick Children
Liana Figueiredo Nobre: The Hospital for Sick Children
Pasqualino de Antonellis: The Hospital for Sick Children
Christopher Dunham: British Columbia Children’s Hospital
Sylvia Cheng: The University of British Columbia
Daniel R. Boué: Nationwide Children’s Hospital
Jonathan L. Finlay: Nationwide Children’s Hospital
Scott L. Coven: Nationwide Children’s Hospital
Inmaculada de Prada: Hospital Universitario Niño Jesús
Marta Perez-Somarriba: Hospital Universitario Niño Jesús
Claudia C. Faria: Hospital de Santa Maria
Michael A. Grotzer: University Children’s Hospital Zurich
Elisabeth Rushing: University Hospital Zurich
David Sumerauer: Charles University and University Hospital Motol
Josef Zamecnik: Charles University and University Hospital Motol
Lenka Krskova: Charles University and University Hospital Motol
Miguel Garcia Ariza: Hospital Cruces
Ofelia Cruz: Hospital Sant Joan de Déu
Andres Morales La Madrid: Hospital Sant Joan de Déu
Palma Solano: Hospital Infantil Virgen del Rocio
Keita Terashima: National Center for Child Health and Development
Yoshiko Nakano: National Cancer Center Research Institute
Koichi Ichimura: National Cancer Center Research Institute
Motoo Nagane: Kyorin University Faculty of Medicine
Hiroaki Sakamoto: Osaka City General Hospital
Maria Joao Gil-da-Costa: University Hospital de São João
Roberto Silva: University Hospital de São João
Donna L. Johnston: Children’s Hospital of Eastern Ontario
Jean Michaud: University of Ottawa
Bev Wilson: University of Alberta
Frank K. H. van Landeghem: University of Alberta
Angelica Oviedo: Dalhousie University
P. Daniel McNeely: IWK Health Centre
Bruce Crooks: IWK Health Centre
Iris Fried: Hadassah Medical Center
Nataliya Zhukova: Royal Children’s Hospital
Jordan R. Hansford: Royal Children’s Hospital
Amulya Nageswararao: Mayo Clinic
Livia Garzia: McGill University
Mary Shago: University of Toronto
Michael Brudno: The Hospital for Sick Children
Meredith S. Irwin: The Hospital for Sick Children
Ute Bartels: The Hospital for Sick Children
Vijay Ramaswamy: The Hospital for Sick Children
Eric Bouffet: The Hospital for Sick Children
Michael D. Taylor: The Hospital for Sick Children
Uri Tabori: The Hospital for Sick Children
Cynthia Hawkins: The Hospital for Sick Children

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Infant 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 kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway 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.

Date: 2019
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DOI: 10.1038/s41467-019-12187-5

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