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    Harmonization of postmortem donations for pediatric brain tumors and molecular characterization of diffuse midline gliomas

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    Author
    Kambhampati, M.
    Panditharatna, E.
    Ho, C.-Y.
    Date
    2020
    Journal
    Scientific Reports
    Publisher
    Nature Research
    Type
    Article
    
    Metadata
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    https://doi.org/10.1038/s41598-020-67764-2
    Abstract
    Children diagnosed with brain tumors have the lowest overall survival of all pediatric cancers. Recent molecular studies have resulted in the discovery of recurrent driver mutations in many pediatric brain tumors. However, despite these molecular advances, the clinical outcomes of high grade tumors, including H3K27M diffuse midline glioma (H3K27M DMG), remain poor. To address the paucity of tissue for biological studies, we have established a comprehensive protocol for the coordination and processing of donated specimens at postmortem. Since 2010, 60 postmortem pediatric brain tumor donations from 26 institutions were coordinated and collected. Patient derived xenograft models and cell cultures were successfully created (76% and 44% of attempts respectively), irrespective of postmortem processing time. Histological analysis of mid-sagittal whole brain sections revealed evidence of treatment response, immune cell infiltration and the migratory path of infiltrating H3K27M DMG cells into other midline structures and cerebral lobes. Sequencing of primary and disseminated tumors confirmed the presence of oncogenic driver mutations and their obligate partners. Our findings highlight the importance of postmortem tissue donations as an invaluable resource to accelerate research, potentially leading to improved outcomes for children with aggressive brain tumors. Copyright 2020, The Author(s).
    Sponsors
    Matthew Larson Foundation for Pediatric Brain; Pediatric Brain Tumor Foundation, PBTF
    Keyword
    Children
    Donation of organs, tissues, etc.
    Biomedical Research
    Glioma--pathology
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087368501&doi=10.1038%2fs41598-020-67764-2&partnerID=40&md5=965558fea5302d180894e3e93d98726a; http://hdl.handle.net/10713/13295
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-020-67764-2
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    UMB Open Access Articles 2020

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