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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-09-25

AUTHORS

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, Cynthia Hawkins

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. More... »

PAGES

4343

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    10

    Author Affiliations

  • Department of Oncology and Children’s Research Center, University Children’s Hospital Zurich, Zurich, Switzerland
  • Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada
  • Department of Hematology and Oncology, The Hospital for Sick Children, Toronto, ON Canada
  • Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic
  • Department of Pediatric Hematology and Oncology, Hospital Universitario Niño Jesús, Madrid, Spain
  • The Arthur and Sonia Labatt Brain Tumor Research Centre, The Hospital for Sick Children, Toronto, ON Canada
  • Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON Canada
  • Centre for Computational Medicine, The Hospital for Sick Children, Toronto, ON Canada
  • Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC Canada
  • Division of Hematology/Oncology/BMT, British Columbia Children’s Hospital, Vancouver, BC Canada
  • Department of Pathology, The Ohio State University College of Medicine, Columbus, OH USA
  • Division of Hematology/Oncology/Bone Marrow Transplantation, Nationwide Children’s Hospital, Columbus, OH USA
  • Department of Pathology, Hospital Universitario Niño Jesús, Madrid, Spain
  • Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
  • Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland
  • Department of Pediatric Oncology, Hospital Cruces, Bilbao, Spain
  • Department of Pediatric Oncology, Hospital Sant Joan de Déu, Barcelona, Spain
  • Department of Pediatric Oncology, Hospital Infantil Virgen del Rocio, Sevilla, Spain
  • Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan
  • Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan
  • Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan
  • Department of Pediatric Neurosurgery, Osaka City General Hospital, Osaka, Japan
  • Division of Pediatric Hematoncology, University Hospital de São João, Porto, Portugal
  • Department of Pathology, University Hospital de São João, Porto, Portugal
  • Division of Hematology/Oncology, Children’s Hospital of Eastern Ontario, Ottawa, ON Canada
  • Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON Canada
  • Department of Pediatrics, University of Alberta, Edmonton, AB Canada
  • Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, AB Canada
  • Department of Pathology Laboratory Medicine, IWK Health Centre, Halifax, NS Canada
  • Division of Neurosurgery, IWK Health Centre, Halifax, NS Canada
  • Division of Hematology-Oncology, IWK Health Centre, Halifax, NS Canada
  • The Department of Pediatric Hematology Oncology, Hadassah Medical Center, Jerusalem, Israel
  • Children’s Cancer Centre, Royal Children’s Hospital, Melbourne, Australia
  • Murdoch Children’s Research Institute, Department of Paediatrics, University of Melbourne, Melbourne, Australia
  • Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, MN USA
  • Department of Medicine, McGill University, Montreal, QC Canada
  • Department of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada
  • Department of Medical Biophysics, University of Toronto, Toronto, ON Canada
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-019-12187-5

    DOI

    http://dx.doi.org/10.1038/s41467-019-12187-5

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1121215814

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31554817


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