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Published in: Journal of Neuro-Oncology 1/2024

25-04-2024 | Medulloblastoma | Research

PUMC-MB1 is a novel group 3 medulloblastoma preclinical model, sensitive to PI3K/mTOR dual inhibitor

Authors: Shizun Wang, Dan Zhang, Jialin Wang, Xiaojiao Peng, Hailang Sun, Yuanqi Ji, Zhenli Yang, Xiaocui Bian, Yuhong Hou, Ming Ge, Yuqin Liu

Published in: Journal of Neuro-Oncology | Issue 1/2024

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Abstract

Purpose

Medulloblastoma (MB), a common and heterogeneous posterior fossa tumor in pediatric patients, presents diverse prognostic outcomes. To advance our understanding of MB’s intricate biology, the development of novel patient tumor-derived culture MB models with necessary data is still an essential requirement.

Methods

We continuously passaged PUMC-MB1 in vitro in order to establish a continuous cell line. We examined the in vitro growth using Cell Counting Kit-8 (CCK-8) and in vivo growth with subcutaneous and intracranial xenograft models. The xenografts were investigated histopathologically with Hematoxylin and Eosin (HE) staining and immunohistochemistry (IHC). Concurrently, we explored its molecular features using Whole Genome Sequencing (WGS), targeted sequencing, and RNA sequecing. Guided by bioinformatics analysis, we validated PUMC-MB1’s drug sensitivity in vitro and in vivo.

Results

PUMC-MB1, derived from a high-risk MB patient, displayed a population doubling time (PDT) of 48.18 h and achieved 100% tumor growth in SCID mice within 20 days. HE and Immunohistochemical examination of the original tumor and xenografts confirmed the classification of PUMC-MB1 as a classic MB. Genomic analysis via WGS revealed concurrent MYC and OTX2 amplifications. The RNA-seq data classified it within the Group 3 MB subgroup, while according to the WHO classification, it fell under the Non-WNT/Non-SHH MB. Comparative analysis with D283 and D341med identified 4065 differentially expressed genes, with notable enrichment in the PI3K-AKT pathway. Cisplatin, 4-hydroperoxy cyclophosphamide/cyclophosphamide, vincristine, and dactolisib (a selective PI3K/mTOR dual inhibitor) significantly inhibited PUMC-MB1 proliferation in vitro and in vivo.

Conclusions

PUMC-MB1, a novel Group 3 (Non-WNT/Non-SHH) MB cell line, is comprehensively characterized for its growth, pathology, and molecular characteristics. Notably, dactolisib demonstrated potent anti-proliferative effects with minimal toxicity, promising a potential therapeutic avenue. PUMC-MB1 could serve as a valuable tool for unraveling MB mechanisms and innovative treatment strategies.
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Literature
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Metadata
Title
PUMC-MB1 is a novel group 3 medulloblastoma preclinical model, sensitive to PI3K/mTOR dual inhibitor
Authors
Shizun Wang
Dan Zhang
Jialin Wang
Xiaojiao Peng
Hailang Sun
Yuanqi Ji
Zhenli Yang
Xiaocui Bian
Yuhong Hou
Ming Ge
Yuqin Liu
Publication date
25-04-2024
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 1/2024
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-024-04655-w

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