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Diffuse Intrinsic Pontine Glioma

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Book cover Pediatric Neuro-oncology

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Abstract

Diffuse intrinsic pontine gliomas (DIPGs) are almost uniformly fatal, predominantly affect children, and are the most common brainstem tumors of childhood. DIPG is diagnosed based on characteristic magnetic resonance imaging (MRI) findings in a child with typical clinical features, and routine biopsy for tissue diagnosis is not currently part of the standard of care. Surgical resection is not considered an option due to critical tumor location, and the beneficial effects of radiation therapy are only transient and at best considered palliative. Chemotherapy, given as single or multiple agents, with and without radiation, has had no demonstrable impact on the outcome of these tumors. Multiple clinical trials using novel treatment strategies and new therapeutic agents have not improved prognosis in the past two decades. Recent integrated genomic studies identify many DIPG as distinct from the pediatric and adult supratentorial high-grade gliomas (HGG). Chromatin remodeling defects in the developing brain due to recurrent somatic driver mutations affecting the histone 3 variant protein, H3.3 (H3.3-K27M) in association with mutations involving specific genes (TP53, PDGFRA, MYC/PVT1) may play a pivotal role in the pathogenesis of DIPG tumors. Future clinical trials should be based on molecular classification of tumor tissue obtained from biopsy, as this will help in better treatment stratification and more specific targeted therapies.

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Acknowledgments

Dr. Issai Vanan is the Father Peter J. Mckenna St. Baldrick’s Cancer Research Scholar, supported by the St. Baldrick’s Foundation, USA. Dr. Eisenstat holds the Muriel and Ada Hole Kids with Cancer Society Chair in Pediatric Oncology, University of Alberta.

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Authors and Affiliations

  1. Departments of Pediatrics and Child Health, Oncology and Cell Biology, Cancer Care Manitoba, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, MB, Canada

    Magimairajan Issai Vanan M.D., M.P.H., F.A.A.P.

  2. Division of Neurosurgery, Department of Surgery, Stollery Children’s Hospital / University of Alberta, Edmonton, AB, Canada

    Vivek Mehta M.D., M.Sc.

  3. Departments of Pediatrics, Medical Genetics and Oncology, Stollery Children’s Hospital, University of Alberta, Edmonton Clinic Health Academy, Edmonton, AB, Canada

    David D. Eisenstat M.D., M.A., F.R.C.P.C.

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  1. Magimairajan Issai Vanan M.D., M.P.H., F.A.A.P.
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  2. Vivek Mehta M.D., M.Sc.
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  3. David D. Eisenstat M.D., M.A., F.R.C.P.C.
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Corresponding author

Correspondence to David D. Eisenstat M.D., M.A., F.R.C.P.C. .

Editor information

Editors and Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, Associate Professor of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada

    Katrin Scheinemann

  2. Department of Haematology/Oncology, Garron Family Chair in Childhood Cancer Research, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    Eric Bouffet

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Vanan, M.I., Mehta, V., Eisenstat, D.D. (2015). Diffuse Intrinsic Pontine Glioma. In: Scheinemann, K., Bouffet, E. (eds) Pediatric Neuro-oncology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1541-5_11

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  • DOI: https://doi.org/10.1007/978-1-4939-1541-5_11

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-1540-8

  • Online ISBN: 978-1-4939-1541-5

  • eBook Packages: MedicineMedicine (R0)

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