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

Author

Listed:
  • Min Wu

    (Chinese Academy of Medical Sciences
    Soochow University
    Shanghai Jiao Tong University School of Medicine
    Nanjing Medical University)

  • Tingting Wang

    (Chinese Academy of Medical Sciences
    Changping Laboratory
    Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Nan Ji

    (Capital Medical University
    Capital Medical University)

  • Ting Lu

    (The First Affiliated Hospital of Soochow University)

  • Ran Yuan

    (Chinese Academy of Medical Sciences
    Soochow University)

  • Lingxiang Wu

    (Nanjing Medical University
    Nanjing Medical University
    Jiangsu Institute of Cancer Research)

  • Junxia Zhang

    (Nanjing Medical University
    The First Affiliated Hospital of Nanjing Medical University)

  • Mengyuan Li

    (Chinese Academy of Medical Sciences
    Changping Laboratory)

  • Penghui Cao

    (Chinese Academy of Medical Sciences)

  • Jiarui Zhao

    (Chinese Academy of Medical Sciences)

  • Guanzhang Li

    (Capital Medical University
    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
    Shanghai University
    Gongli Hospital of Shanghai Pudong New Area)

  • 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
    The First Affiliated Hospital of Nanjing Medical University)

  • Wei Zhang

    (Capital Medical University
    Capital Medical University
    Capital Medical University)

  • Qianghu Wang

    (Nanjing Medical University
    Nanjing Medical University
    Jiangsu Institute of Cancer Research)

  • Jian Chen

    (Chinese Academy of Medical Sciences
    Changping Laboratory
    Chinese Academy of Medical Sciences & Peking Union Medical College)

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.

Suggested Citation

  • 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 , 2024. "Multi-omics and pharmacological characterization of patient-derived glioma cell lines," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51214-y
    DOI: 10.1038/s41467-024-51214-y
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    References listed on IDEAS

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