脉络丛（ChP）是位于脑室的分泌性上皮结构。脉络丛肿瘤（CPT）是一种罕见的肿瘤，主要发生在儿童中恶性程度加剧的年轻患者中。对肿瘤病理学的了解不足和有效模型的可用性有限，阻碍了 CPT 治疗。分析了 CPT 患者的基因组和转录组数据，以确定假定的病理途径。采用细胞和分子技术来验证 CPT 患者样本的生物信息学结果。在 CPT 细胞中评估了 Wnt/β-连环蛋白信号传导的药理学抑制。在 CRISPR-Cas9 衍生的 Wnt/β-连环蛋白途径基因敲除和过度表达后，对 ChP 细胞系进行了基于细胞的测定。 3D CPT 模型是通过 CRISPR-Cas9 衍生的 APC 敲除生成的。我们发现 Wnt/β-catenin 信号在人类 CPT 中被激活，这可能是 CPT 基因组大规模染色体不稳定事件的结果。我们证明 CPT 衍生细胞的生存依赖于自分泌 Wnt/β-连环蛋白信号传导。通过敲除负调节因子 APC 或过度表达配体 WNT3A，组成型 Wnt/β-catenin 通路激活可在 ChP 2D 体外模型中诱导致瘤特性。通过使用有效的 GSK3β 抑制剂处理，ChP 类器官中 Wnt/β-catenin 通路的激活增加，从而减少了成熟 ChP 上皮细胞的分化。值得注意的是，APC 的消耗足以诱导 ChP 类器官的致癌转化。我们的研究确定 Wnt/β-catenin 信号传导是 CPT 肿瘤发生的关键驱动因素，并为未来 CPT 的病理和治疗研究提供了第一个 3D 体外模型。 © 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Choroid plexus (ChP) is the secretory epithelial structure located in brain ventricles. Choroid plexus tumors (CPTs) are rare neoplasms predominantly occurring in young patients with intensified malignancy in children. CPT treatment is hindered by insufficient knowledge of the tumor pathology and limited availability of valid models.Genomic and transcriptomic data from CPT patients were analyzed to identify the putative pathological pathway. Cellular and molecular techniques were employed to validate bioinformatic results in CPT patient samples. Pharmacologic inhibition of Wnt/β-catenin signaling was assessed in CPT cells. Cell-based assays of ChP cell lines were performed following CRISPR-Cas9-derived knockout and over-expression of Wnt/β-catenin pathway genes. 3D CPT model was generated through CRISPR-Cas9-derived knockout of APC.We discovered that Wnt/β-catenin signaling is activated in human CPTs, likely as a consequence of large-scale chromosomal instability events of the CPT genomes. We demonstrated that CPT-derived cells depend on autocrine Wnt/β-catenin signaling for survival. Constitutive Wnt/β-catenin pathway activation, either through knock-out of the negative regulator APC or overexpression of the ligand WNT3A, induced tumorigenic properties in ChP 2D in vitro models. Increased activation of Wnt/β-catenin pathway in ChP organoids, through treatment with a potent GSK3β inhibitor, reduced the differentiation of mature ChP epithelia cells. Remarkably, the depletion of APC was sufficient to induce the oncogenic transformation of ChP organoids.Our research identifies Wnt/β-catenin signaling as a critical driver of CPT tumorigenesis and provides the first 3D in vitro model for future pathological and therapeutic studies of CPT.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.