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Frequent Co‐Alterations of TP53, p16/CDKN2A, p14 ARF , PTEN Tumor Suppressor Genes in Human Glioma Cell Lines.
Open accessAbstract
In this study we established the simultaneous status of TP53, p16, p14ARF and PTEN tumor suppressor genes in 34 randomly chosen human glioma cell lines. Nine cell lines (26.4%) harbored mutations or deletions in all four tumor suppressor genes and 22 cell lines (64%) had alterations in at least three. Mutations/deletions were found at the following frequencies: TP53 (76.5%), p14ARF (64.7%), p16 (64.7%), PTEN (73.5%). Thus, there was a high incidence of alterations in the cellular pathways involving the p53 transcription factor (94.1%), the retinoblastoma protein (64.7%) and the PTEN phosphatase (73.5%) and 91% of cell lines carried mutations in two or more pathways. This provides the first clear genetic evidence that these tumor suppressors participate in biological pathways which are functioning separately/independently in glioma cells. The status of the gene alterations did not correlate with tumorigenicity in immunocompromized mice or any clinical parameters. Although the mutation rate was higher in glioma cell lines than that reported for glioma tissues, the alterations were molecularly representative of those found in adult de novo glioblastoma. This study highlights the importance of developing therapeutic approaches applicable to tumors with a broad range of genetic alterations and also provides an invaluable panel of glioma cell lines to make this possible.
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“The p53-ARF-MDM2 pathway is deregulated in 84% of glioblastoma (GBM) patients and 94% of GBM cell lines.”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [20]
In the citing paper
“In these experiments, we used tumorigenic U87 cells, a common model of human gliomas (23).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [23]
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Metadata
- Authors
- Ishii, N., Maier, D., Merlo, A., Tada, M., Sawamura, Y., Diserens, A., & Van Meir, E. G.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- University Hospital of Basel (CH)
- Hokkaido University (JP)
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 1999-07
- Volume
- 9
- Issue
- 3
- Pages
- 469-479
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC8098486
- OpenAlex
- W2155140015
- Cited by
- 569
- References
- 48
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 24 · 2023: 20 · 2022: 21 · 2021: 23 · 2020: 13 · 2019: 25 · 2018: 14 · 2017: 16 · 2016: 14 · 2015: 27 · 2014: 33 · 2013: 25 · 2012: 34
- FWCI
- 11.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- glioma cell lines, TP53 mutation, CDKN2A/p16, p14ARF, PTEN, p53 pathway, glioblastoma, tumorigenicity, genetic alterations
- MeSH terms
- Adult, Aged, Animals, Brain Neoplasms, Child, DNA Mutational Analysis, Female, Glioma, Humans, Male, Mice, Nude, Middle Aged, Neoplasm Transplantation, Neoplastic Processes, Phosphoric Monoester Hydrolases, Proteins, Sex Factors, Tumor Cells, Cultured, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Point Mutation, Sequence Deletion, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Proteins, Tumor Suppressor Protein p14ARF, PTEN Phosphohydrolase, Mice
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