Journal
ACTA NEUROPATHOLOGICA
Volume 140, Issue 2, Pages 209-225Publisher
SPRINGER
DOI: 10.1007/s00401-020-02171-5
Keywords
PDOX; Pediatric brain tumors; Medulloblastoma; Ependymoma; AT; RT; ETMR
Categories
Funding
- National Cancer Institute grants [PO1-CA-096832, RO1CA232143-01]
- Brain Tumor Charity (Quest for Cures and Clinical Biomarkers)
- American Lebanese Syrian Associated Charities (ALSAC)
- Sontag Foundation Distinguish Scientist Award
- [CA-P30 CA021765]
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Pediatric brain tumors are the leading cause of cancer-related death in children. Patient-derived orthotopic xenografts (PDOX) of childhood brain tumors have recently emerged as a biologically faithful vehicle for testing novel and more effective therapies. Herein, we provide the histopathological and molecular analysis of 37 novel PDOX models generated from pediatric brain tumor patients treated at St. Jude Children's Research Hospital. Using a combination of histopathology, whole-genome and whole-exome sequencing, RNA-sequencing, and DNA methylation arrays, we demonstrate the overall fidelity and inter-tumoral molecular heterogeneity of pediatric brain tumor PDOX models. These models represent frequent as well as rare childhood brain tumor entities, including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumor, and embryonal tumor with multi-layer rosettes. PDOX models will be valuable platforms for evaluating novel therapies and conducting pre-clinical trials to accelerate progress in the treatment of brain tumors in children. All described PDOX models and associated datasets can be explored using an interactive web-based portal and will be made freely available to the research community upon request.
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