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

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.

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Publication Details

Journal
Nature Communications
Published
2024-08-08
DOI
https://doi.org/10.1038/s41467-024-51214-y
Citations
23
Primary Topic
Glioma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
9.63
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Multi-omics and pharmacological characterization of patient-derived glioma cell lines

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23 citations
Nature Communications
Glioma Diagnosis and Treatment
9.63
article

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

Yongping You, Qianghu Wang, Guanzhang Li, Zhengliang Gao, Penghui Cao, Ting Lu, Ran Yuan, Anhua Wu, Yujie Tang, Min Wu, Nan Ji, Ming Ge, Wen Cheng, Jian Chen, Yu Li, Mengyuan Li, Wei Zhang, Tingting Wang, Rui Li, Jianyu Li, Junxia Zhang, Gang Cui, Jiarui Zhao, Lingxiang Wu, Xiuxing Wang
article en
23 citations

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.

Nature CommunicationsVol. 15(1)
Shanghai University (CN), Shanghai Jiao Tong University (CN), Capital Medical University (CN), Nantong University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Renji Hospital (CN), China-Japan Friendship Hospital (CN), Soochow University (CN), Affiliated Hospital of Nantong University (CN), Beijing Tian Tan Hospital (CN), National Clinical Research Center for Digestive Diseases (CN), Changji University (CN), Nanjing Brain Hospital (CN), Beijing Institute of Neurosurgery (CN), Chinese Institute for Brain Research (CN), Jiangsu Cancer Hospital (CN), Beijing Children’s Hospital (CN), Shanghai Sunshine Rehabilitation Center (CN), Shanghai Pudong New Area Gongli Hospital (CN), Jiangsu Province Hospital (CN), First Affiliated Hospital of Soochow University (CN), Nanjing Medical University (CN), China Medical University (CN)
Zero hunger
Openalex Percentile: Top 1%
Glioma Diagnosis and Treatment
9.63
DOIOpen Access PDFOpenAlex
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