Multi-omics and pharmacological characterization of patient-derived glioma cell lines

Min Wu, Tingting Wang, Nan Ji, Ting Lu, Ran Yuan, Lingxiang Wu, Junxia Zhang, Mengyuan Li, Penghui Cao, Jiarui Zhao, Guanzhang Li, Jianyu Li, Yu Li, Yujie Tang, Zhengliang Gao, Xiuxing Wang, Wen Cheng, Ming Ge, Gang Cui, Rui Li, Anhua Wu, Yongping You (), Wei Zhang (), Qianghu Wang () and Jian Chen ()
Additional contact information
Min Wu: Chinese Academy of Medical Sciences
Tingting Wang: Chinese Academy of Medical Sciences
Nan Ji: Capital Medical University
Ting Lu: The First Affiliated Hospital of Soochow University
Ran Yuan: Chinese Academy of Medical Sciences
Lingxiang Wu: Nanjing Medical University
Junxia Zhang: Nanjing Medical University
Mengyuan Li: Chinese Academy of Medical Sciences
Penghui Cao: Chinese Academy of Medical Sciences
Jiarui Zhao: Chinese Academy of Medical Sciences
Guanzhang Li: Capital Medical University
Jianyu Li: Chinese Academy of Medical Sciences
Yu Li: Chinese Academy of Medical Sciences
Yujie Tang: Shanghai Jiao Tong University School of Medicine
Zhengliang Gao: Tongji University
Xiuxing Wang: Nanjing Medical University
Wen Cheng: Shengjing Hospital of China Medical University
Ming Ge: National Center for Children’s Health
Gang Cui: The First Affiliated Hospital of Soochow University
Rui Li: Chaoyang District
Anhua Wu: Shengjing Hospital of China Medical University
Yongping You: Nanjing Medical University
Wei Zhang: Capital Medical University
Qianghu Wang: Nanjing Medical University
Jian Chen: Chinese Academy of Medical Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.

Date: 2024
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DOI: 10.1038/s41467-024-51214-y

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