Cited by 146Cancer-related Molecular PathwaysGlioma Diagnosis and TreatmentChromatin Remodeling and Cancer

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p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive events in human glioblastoma

Fulci, Giulia, Labuhn, Martin, Maier, Daniel, Lachat, Yan, Hausmann, Oliver, Hegi, Monika E, Janzer, Robert C, Merlo, Adrian, Van Meir, Erwin G·2000·Oncogene

DOI 10.1038/sj.onc.1203700

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Abstract

P16 and P14ARF are two tumor suppressors encoded by the locus ink4a-arf which is frequently deleted in human tumors. Recent experiments performed with mouse embryonic fibroblasts have shown that P14ARF is an upstream regulator of the P53 pathway. This raises the question as to whether in human tumors the loss of p14arf and mutation of p53 are mutually exclusive events which segregate with genetic alterations at other loci. To examine this question we performed a multigenic analysis on 29 gliomas. We analysed p53 and p14arf in relation with five other genetic loci encoding the most frequently mutated genes in human gliomas: cdkn2a, mdm2, egfr, pten and the chromosomal regions 10q23.3 and 10q25-26. Our study shows for the first time that p53 mutations and p14arf deletions appear mutually exclusive in human glioblastoma, suggesting that they may be functionally redundant in glioma tumorigenesis. The P53 pathway is, therefore, disrupted in 81.8% of malignant gliomas (WHO grades III and IV), either by mutation of the p53 gene (31.8%) or by p14arf deletion (54.5%). These tumors further showed MDM2 overexpression (9.1%), egfr oncogene amplification/egfr overexpression (50%), pten mutations (27.3%) and loss of heterozygosity (LOH) at the chromosomal regions 10q23.3 (86.4%) and 10q25-26 (100%). These alterations did not segregate with p53 mutations or p14arf deletions, while p14arf and cdkn2a were always deleted.

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Authors: Fulci, G., Labuhn, M., Maier, D., Lachat, Y., Hausmann, O., Hegi, M. E., Janzer, R. C., Merlo, A., & Van Meir, E. G.
Affiliations: Centre Hospitalier Universitaire Vaudois (CH)
University Hospital of Basel (CH)
ORCID: Fulci, Giulia
Hausmann, Oliver
Hegi, Monika E
Venue: Oncogene
Publisher: Springer Science and Business Media LLC
Published: 2000-07-28
Volume: 19
Issue: 33
Pages: 3816-3822
ISSN: 0950-9232 (ISSN-L)
1476-5594
DOI: 10.1038/sj.onc.1203700
OpenAlex: W2069294039
Cited by: 146
References: 41
Citations by year: 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 7 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 4 · 2012: 7
FWCI: 7.04
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Oncogene (publishedVersion)
PubMed (publishedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: glioblastoma, TP53 mutation, INK4a/ARF locus, tumor suppressor, MDM2 overexpression, EGFR amplification, PTEN mutation, CDKN2A, loss of heterozygosity, p53 pathway
MeSH terms: Animals, Carrier Proteins, Glioblastoma, Humans, Nuclear Proteins, Phosphoric Monoester Hydrolases, Proteins, Proto-Oncogene Proteins, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Mutagenesis, Gene Deletion, Cyclin-Dependent Kinase Inhibitor p16, Tumor Suppressor Proteins, Tumor Suppressor Protein p14ARF, PTEN Phosphohydrolase, Mice, Proto-Oncogene Proteins c-mdm2, ErbB Receptors

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p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive events in human glioblastoma

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