Spatial and temporal homogeneity of driver mutations in diffuse intrinsic pontine glioma

Hamid Nikbakht, Eshini Panditharatna, Leonie G. Mikael, Rui Li, Tenzin Gayden, Matthew Osmond, Cheng-Ying Ho, Madhuri Kambhampati, Eugene I. Hwang, Damien Faury, Alan Siu, Simon Papillon-Cavanagh, Denise Bechet, Keith L. Ligon, Benjamin Ellezam, Wendy J. Ingram, Caedyn Stinson, Andrew S. Moore, Katherine E. Warren, Jason Karamchandani, Roger J. Packer, Nada Jabado (), Jacek Majewski () and Javad Nazarian ()
Additional contact information
Hamid Nikbakht: McGill University
Eshini Panditharatna: Research Center for Genetic Medicine, Children’s National Health System
Leonie G. Mikael: McGill University and McGill University Heath Centre Research Institute
Rui Li: McGill University
Tenzin Gayden: McGill University
Matthew Osmond: McGill University
Cheng-Ying Ho: Children’s National Health System
Madhuri Kambhampati: Research Center for Genetic Medicine, Children’s National Health System
Eugene I. Hwang: Center for Cancer and Blood Disorders, Children’s National Health System
Damien Faury: McGill University and McGill University Heath Centre Research Institute
Alan Siu: George Washington University School of Medicine and Health Sciences
Simon Papillon-Cavanagh: McGill University
Denise Bechet: McGill University
Keith L. Ligon: Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute
Benjamin Ellezam: CHU Ste-Justine, Université de Montréal
Wendy J. Ingram: UQ Child Health Research Centre, The University of Queensland
Caedyn Stinson: University of Queensland Diamantina Institute, The University of Queensland
Andrew S. Moore: UQ Child Health Research Centre, The University of Queensland
Katherine E. Warren: National Cancer Institute, National Institute of Health
Jason Karamchandani: Montreal Neurological Hospital, McGill University
Roger J. Packer: Brain Tumour Institute, Center for Neuroscience and Behavioral Medicine, Children’s National Health System
Nada Jabado: McGill University
Jacek Majewski: McGill University
Javad Nazarian: Research Center for Genetic Medicine, Children’s National Health System

Nature Communications, 2016, vol. 7, issue 1, 1-8

Abstract: Abstract Diffuse Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guide diagnosis and targeted therapies. To address spatial heterogeneity, here we analyse 134 specimens from various neuroanatomical structures of whole autopsy brains from nine DIPG patients. Evolutionary reconstruction indicates histone 3 (H3) K27M—including H3.2K27M—mutations potentially arise first and are invariably associated with specific, high-fidelity obligate partners throughout the tumour and its spread, from diagnosis to end-stage disease, suggesting mutual need for tumorigenesis. These H3K27M ubiquitously-associated mutations involve alterations in TP53 cell-cycle (TP53/PPM1D) or specific growth factor pathways (ACVR1/PIK3R1). Later oncogenic alterations arise in sub-clones and often affect the PI3K pathway. Our findings are consistent with early tumour spread outside the brainstem including the cerebrum. The spatial and temporal homogeneity of main driver mutations in DIPG implies they will be captured by limited biopsies and emphasizes the need to develop therapies specifically targeting obligate oncohistone partnerships.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11185

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DOI: 10.1038/ncomms11185

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