Deregulation of the p14ARF/Mdm2/p53 pathway and G1/S transition in two glioblastoma sets
Abstract
Sixty-one glioblastomas have been studied, subdivided into the categories of classic glioblastomas (GBM) and glioblastomas with astrocytic (GBA) and oligodendroglial (GBO) differentiated areas. On surgical samples, TP53, Mdm2, CDKN2A/p16-p14 alterations were studied by molecular biology techniques and by immunohistochemistry. It has been found that Mdm2 amplification was more frequent in GBM than in GBA and GBO, that p14ARF was inactivated in a high percentage of cases in the three tumor categories. Both these and other alterations did not reach a statistical significance, with the exception of CDKN2A/p16 homozygous deletion which showed the highest frequency in GBO. The latter finding could be in line with the observation that CDKN2A/p16 inactivation is a step in the molecular pathway to tumor progression in oligodendrogliomas. TP53 mutations and Mdm2 amplifications were mutually exclusive, whereas TP53 mutations and CDKN2A/p14 inactivation coexisted in 5 cases. The alterations of the p53/Mdm2/p14ARF pathway occurred in 73% of cases and in 80% of cases if CDKN2A homozygous deletions were associated. All glioblastomas with gemistocytic areas showed p14ARF inactivation. Immunohistochemistry showed higher percentages of positivity in comparison with molecular genetics, but with similar variations.
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ARF deletion is correlated with overexpression of TCTN1, a protein involved in promotion of glioblastoma cell proliferation.
“ARF deletion is correlated with overexpression of tectonic family member 1 (TCTN1), a protein involved in a diverse range of cellular processes, including promotion of GBM cell proliferation.”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [38]
MDM2 amplifications are more common in classic glioblastomas when compared to glioblastomas with astrocytic and oligodendroglial differentiated areas.
“MDM2 amplifications are more common in classic GBMs when compared to GBMs with astrocytic and oligodendroglial differentiated areas [38].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [38]
MDM2 amplifications and TP53 mutations are mutually exclusive.
“MDM2 amplifications and TP53 mutations are mutually exclusive [38].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [38]
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The p53 Pathway in Glioblastoma
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- Authors
- Ghimenti, C., Fiano, V., Chiadò-Piat, L., Chiò, A., Cavalla, P., & Schiffer, D.
- Affiliations
- University of Turin (IT)
- Venue
- Journal of Neuro-Oncology
- Published
- 2003-01
- Volume
- 61
- Issue
- 2
- Pages
- 95-102
- ISSN
- 0167-594X (ISSN-L)
- 1573-7373
- OpenAlex
- W1571160073
- Cited by
- 21
- References
- 35
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2015: 1 · 2012: 1
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- glioblastoma, p14ARF, MDM2, p53 pathway, CDKN2A/p16, G1/S transition, MDM2 amplification, TP53 mutation, oligodendroglioma, astrocyte differentiation, tumor progression, tumor heterogeneity
- MeSH terms
- Brain Neoplasms, DNA Mutational Analysis, Exons, Glial Fibrillary Acidic Protein, Glioblastoma, Humans, Immunoenzyme Techniques, Nuclear Proteins, Proto-Oncogene Proteins, Tumor Cells, Cultured, Tumor Suppressor Protein p53, G1 Phase, S Phase, Sequence Deletion, DNA Methylation, Cyclin-Dependent Kinase Inhibitor p16, Gene Silencing, Tumor Suppressor Protein p14ARF, Proto-Oncogene Proteins c-mdm2
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