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Harmonization of Post-mortem Donations for Pediatric Brain Tumors and Molecular Characterization of Difuse Midline Gliomas

Children diagnosed with brain tumors have the lowest overall survival of all pediatric cancers.  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. Read Full Publication

Dr. Monje-Deisseroth and her team at Stanford University recently published a paper detailing how gliomas are able to “hijack” the brain's communication system.

Published in  Nature: High-grade gliomas are lethal brain cancers whose progression is robustly regulated by neuronal activity. Activity-regulated release of growth factors promotes glioma growth, but this alone is insufficient to explain the effect that neuronal activity exerts on glioma progression. Here we show that neuron and glioma interactions include electrochemical communication through bona fide AMPA receptor-dependent neuron–glioma synapses. Read More

Congratulations to two of our Center of Excellence teams lead by Dr Javad Nazarian and Dr. Michelle Monje on their recent groundbreaking research publication. Due in part to increased access to post-mortem tissuethe teams were able to study a larger sample of DIPG tumors.  Diffuse intrinsic pontine glioma is a lethal pediatric brain cancer characterized by H3K27M histone mutation. Nagaraja et al. characterize a large cohort of rare primary tumors and normal pontine tissue to reveal active regulatory element heterogeneity dependent upon the histone variant and cell context in which the mutation occurs. Read More