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

Details

Serval ID
serval:BIB_DAEA190683FA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
p53 gene mutation and ink4a-arf deletion appear to be two mutually exclusive events in human glioblastoma
Journal
Oncogene
Author(s)
Fulci  G., Labuhn  M., Maier  D., Lachat  Y., Hausmann  O., Hegi  M. E., Janzer  R. C., Merlo  A., Van Meir  E. G.
ISSN
0950-9232 (Print)
Publication state
Published
Issued date
08/2000
Volume
19
Number
33
Pages
3816-22
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 3
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.
Keywords
Animals Carrier Proteins/*genetics Cyclin-Dependent Kinase Inhibitor p16 Gene Deletion *Genes, Tumor Suppressor Glioblastoma/*genetics Humans Mice Mutagenesis *Nuclear Proteins PTEN Phosphohydrolase Phosphoric Monoester Hydrolases/genetics Proteins/*genetics Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-mdm2 Receptor, Epidermal Growth Factor/genetics Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53/*genetics *Tumor Suppressor Proteins
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:06
Last modification date
20/08/2019 17:00
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