Abstract
Abstract Pediatric high-grade gliomas (pHGG) are one of the leading causes of brain cancer deaths in children. Progress towards the characterization of molecular and genetic features in adult high-grade gliomas and subsequent therapies has not yielded similar results in pHGG patients. pHGGs do not readily establish in culture and there has also been a lack of preclinical models to identify new therapeutic targets. Here, we employ a direct brain-to-brain workflow enabling the establishment of rare pediatric tumors including Atypical Teratoid/Rhabdoid Tumor (ATRT), H3_K27ALT diffuse midline gliomas, and H3_G34MUT diffuse hemispheric xenograft models. These Direct, Patient-Derived Orthotopic Xenografts (DPDOX) models recapitulate the clinical, genomic, and transcriptomic landscape of that of the parental tumors. Moreover, we have incorporated each tumor with a secreted gaussia luciferase reporter enabling the minimally-invasive tracking of intracranial tumor burden over time in response to drug perturbations. Taken together, we present a novel approach to establish pHGG models and evaluate new therapeutics.
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