Journal
EMBO MOLECULAR MEDICINE
Volume -, Issue -, Pages -Publisher
WILEY
DOI: 10.15252/emmm.202318199
Keywords
brain tumors; organoids; patient-derived; pediatric cancer; translational applications
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This study presents a protocol for efficient generation, expansion, and biobanking of pediatric brain cancer organoids. These organoids recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors. The study also shows that the organoids respond similarly to the same therapeutic regimens as the patients. These findings highlight the potential of organoids for research and personalized medicine.
Brain tumors are the leading cause of cancer-related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient-derived organoids (PDOs) from ependymomas, medulloblastomas, low-grade glial tumors, and patient-derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine. imagePatient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) have been established through direct in vitro culture of primary tumors and patient-derived xenograft (PDX)-derived tumors with the goal to better model pediatric tumors of the central nervous system.PDOs recapitulate cellular heterogeneity, histological features, mutational profiles (number of variants, microsatellite instability, tumor mutational burden) of the corresponding parental tumor even after 1 year of in vitro cultureZFTA-RELA EPN- and G3 MB-PDOs recapitulate patients' response to routinely applied therapeutic regimensSeveral PDOs and PDXOs were derived from human tumors for which there are currently very limited in vivo and in vitro models availablePDOs and PDXOs are available to the research community, and can be subjected to genetic manipulations, to drug screening, and translational applications for personalized medicine Patient-derived organoids (PDOs) and patient-derived xenograft organoids (PDXOs) have been established through direct in vitro culture of primary tumors and patient-derived xenograft (PDX)-derived tumors with the goal to better model pediatric tumors of the central nervous system.image
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