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.

中文翻译：

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患者和异种移植衍生的类器官概括了儿科脑肿瘤的特征和患者治疗

脑肿瘤是儿童癌症相关死亡的主要原因。忠实捕捉儿科脑癌特征和肿瘤异质性的实验体外模型有限且难以建立。我们提出了一种协议，可以有效生成、扩展和生物样本库小儿脑癌类器官。利用我们的方案，我们建立了来自室管膜瘤、髓母细胞瘤、低级别胶质瘤的患者来源的类器官（PDO），以及来自髓母细胞瘤异种移植物的患者来源的异种移植类器官（PDXO）。PDO 和 PDXO 概括了它们来源的肿瘤的组织学特征、DNA 甲基化谱和瘤内异质性。我们还表明 PDO 可以异种移植。最有趣的是，当接受相同的常规治疗方案时，PDO 对患者的反应相似。总而言之，我们的研究强调了 PDO 和 PDXO 在个性化医疗研究和转化应用方面的潜力。