Patient-derived orthotopic xenografts of pediatric brain tumors: a St. Jude resource.

Acta Neuropathologica
Kyle S SmithMartine F Roussel

Abstract

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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Citations

Dec 5, 2020·Trends in Genetics : TIG·Jesus Garcia-LopezPaul A Northcott
Mar 23, 2021·Frontiers in Immunology·Darel Martínez BedoyaDenis Migliorini
Apr 20, 2021·Frontiers in Oncology·Zhiqin Li, Sigrid A Langhans
Jan 8, 2021·Cancer Discovery·Clay McLeodJinghui Zhang
Sep 26, 2021·Cancer Research·Troy A McEachron, Lee J Helman
Dec 21, 2021·EMBO Molecular Medicine·Loretta M S LauGlenn M Marshall

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Methods Mentioned

BETA
surgical resection
xenografts
DNA assay
exome sequencing
RNA-seq
surgical resections
surgical
biopsies
xenograft

Software Mentioned

- Count
Illumina Genome Studio
STAR
ComplexHeatmaps
Jude
DESeq
learn
scikit
SAMtools
Conumee Bioconductor

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