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Multi-omics and pharmacological characterization of patient-derived glioma cell lines.
- Source :
-
Nature communications [Nat Commun] 2024 Aug 08; Vol. 15 (1), pp. 6740. Date of Electronic Publication: 2024 Aug 08. - Publication Year :
- 2024
-
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.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Animals
Cell Line, Tumor
Mice
Oxidative Phosphorylation drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Glioblastoma genetics
Glioblastoma pathology
Glioblastoma drug therapy
Glioblastoma metabolism
Female
Male
Whole Genome Sequencing
Xenograft Model Antitumor Assays
Genomics methods
Gene Expression Regulation, Neoplastic drug effects
Multiomics
Brain Neoplasms pathology
Brain Neoplasms genetics
Brain Neoplasms drug therapy
Brain Neoplasms metabolism
Glioma genetics
Glioma pathology
Glioma drug therapy
Glioma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39112531
- Full Text :
- https://doi.org/10.1038/s41467-024-51214-y