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

Author

Listed:
  • Ana S. Guerreiro Stucklin

    (The Hospital for Sick Children
    The Hospital for Sick Children
    The Hospital for Sick Children
    University Children’s Hospital Zurich)

  • Scott Ryall

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Kohei Fukuoka

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Michal Zapotocky

    (The Hospital for Sick Children
    The Hospital for Sick Children
    Charles University and University Hospital Motol)

  • Alvaro Lassaletta

    (The Hospital for Sick Children
    Hospital Universitario Niño Jesús)

  • Christopher Li

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Taylor Bridge

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Byungjin Kim

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • 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
    The Hospital for Sick Children)

  • Liana Figueiredo Nobre

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Pasqualino de Antonellis

    (The Hospital for Sick Children
    The Hospital for Sick Children)

  • Christopher Dunham

    (British Columbia Children’s Hospital
    The University of British Columbia)

  • Sylvia Cheng

    (The University of British Columbia
    British Columbia Children’s Hospital)

  • Daniel R. Boué

    (Nationwide Children’s Hospital
    The Ohio State University College of Medicine)

  • 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
    Universidade de Lisboa)

  • 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
    IWK Health Centre)

  • 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
    University of Melbourne)

  • Amulya Nageswararao

    (Mayo Clinic)

  • Livia Garzia

    (McGill University)

  • Mary Shago

    (University of Toronto
    Department of Pediatric Laboratory Medicine, The Hospital for Sick Children)

  • 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
    The Hospital for Sick Children)

  • Eric Bouffet

    (The Hospital for Sick Children)

  • Michael D. Taylor

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto
    The Hospital for Sick Children)

  • Uri Tabori

    (The Hospital for Sick Children
    The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto)

  • Cynthia Hawkins

    (The Hospital for Sick Children
    The Hospital for Sick Children
    University of Toronto
    Department of Pediatric Laboratory Medicine, The Hospital for Sick Children)

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.

Suggested Citation

  • 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 & Mon, 2019. "Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12187-5
    DOI: 10.1038/s41467-019-12187-5
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