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Molecular Analysis of the PTEN, TP53 and CDKN2A Tumor Suppressor Genes in Long-term Survivors of Glioblastoma Multiforme
Abstract
Despite multimodal therapy, glioblastoma multiforme (GBM) is associated with a poor prognosis with a median survival of less than 1 year. However, a small number of patients with GBM shows survival times of several years. Although clinical features like age and performance status at diagnosis are well known prognostic parameters, molecular markers for prognosis of overall survival are still lacking. Therefore, we compared 2 age- and gender-matched groups of GBM patients with different post-operative time to tumor progression (TTP), defined as 'short-term' for TTP of less than 6 months (n = 21), and 'long-term' for TTP of more than 24 months (n = 21) for genetic alterations of the PTEN, CDKN2A and TP53 genes as well as overexpression of the EGFR, p53 and Mdm2 proteins. For the GBMs with 'short-term' TTP vs. 'long-term' TTP, the studies revealed PTEN mutations in 4/21 vs. 2/21, TP53 mutations in 5/21 vs. 8/21, homozygous deletion of the CDKN2A gene in 5/21 vs. 6/21, overexpression of EGFR in 7/20 vs. 10/20, accumulation of p53 protein in 9/20 vs. 7/20 and of Mdm2 protein in 0/20 vs. 1/20 cases studied. Taken together, our data indicate that mutations of the PTEN and TP53 tumor suppressor genes, homozygous deletion of the CDKN2A gene as well as overexpression of the EGFR, p53 and Mdm2 proteins lack prognostic significance for overall survival time in patients with GBMs.
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The mutational status of TP53 and its pathway elements ARF-MDM2/4 has not been correlated with survival in glioblastoma, despite the high mutation frequency.
“Although mut-p53 has been correlated to poorer prognosis in breast and other cancers [32], the mutational status of TP53 and its various pathway elements (ARF-MDM2/4) has not been correlated with survival in GBM, despite the high mutation frequency [27,32,33,34].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [34]
CDKN2A/ARF loss has not been shown to correlate with glioblastoma prognosis and/or survival.
“CDKN2A/ARF loss has not been shown to correlate with GBM prognosis and/or survival [27,32,33,34].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [34]
MDM2 amplifications have not been shown to correlate with glioblastoma survival and/or prognosis.
“MDM2 amplifications have not been shown to correlate with GBM survival and/or prognosis [27,32,33,34].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [34]
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Metadata
- Authors
- Kraus, J. A., Glesmann, N., Beck, M., Krex, D., Klockgether, T., Schackert, G., & Schlegel, U.
- Affiliations
- University of Bonn (DE)
- Technische Universität Dresden (DE)
- Venue
- Journal of Neuro-Oncology
- Published
- 2000-06
- Volume
- 48
- Issue
- 2
- Pages
- 89-94
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- OpenAlex
- W1532514239
- Cited by
- 100
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 5 · 2012: 1
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Krebshilfe
- Dr. Mildred Scheel Stiftung für Krebsforschung
- Topics
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Keywords
- glioblastoma, PTEN, TP53, CDKN2A, tumor suppressor, EGFR overexpression, p53 accumulation, MDM2, time to tumor progression, long-term survival, prognostic factors, homozygous deletion, genetic mutations
- MeSH terms
- Adult, DNA Mutational Analysis, DNA, Neoplasm, Female, Glioblastoma, Humans, Male, Middle Aged, Neoplasm Proteins, Phosphoric Monoester Hydrolases, Postoperative Period, Prognosis, Supratentorial Neoplasms, Survival Analysis, Genes, Tumor Suppressor, Genes, p53, Gene Deletion, Survivors, Disease-Free Survival, Polymorphism, Single-Stranded Conformational, Cyclin-Dependent Kinase Inhibitor p16, Genes, p16, Tumor Suppressor Proteins, PTEN Phosphohydrolase
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