Hemizygous or homozygous deletion of the chromosomal region containing the p16INK4a gene is associated with amplification of the EGF receptor gene in glioblastomas

Détails

ID Serval
serval:BIB_D0C7ADCEB971
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Hemizygous or homozygous deletion of the chromosomal region containing the p16INK4a gene is associated with amplification of the EGF receptor gene in glioblastomas
Périodique
International Journal of Cancer
Auteur⸱e⸱s
Hegi  M. E., zur Hausen  A., Ruedi  D., Malin  G., Kleihues  P.
ISSN
0020-7136 (Print)
Statut éditorial
Publié
Date de publication
09/1997
Volume
73
Numéro
1
Pages
57-63
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Sep 26
Résumé
The p16INK4a gene product acts as a negative regulator of the cell cycle by binding to cyclin-dependent kinases (CDKs) 4 and 6, thereby inhibiting the formation of an active CDK/cyclin D complex. Deletion of the p16 locus has been observed in tumor cell lines and, less frequently, in primary human neoplasms. We analyzed 31 glioblastomas and identified 6 cases with hemizygous and 6 with homozygous deletions of the p16 locus. Eight of these cases showed a concurrent amplification of the EGFR gene (epidermal growth factor receptor) while the overall frequency was 35%. This close correlation suggests that deletion of the p16 chromosomal region constitutes another genetic hallmark of the primary glioblastoma, which rapidly develops de novo, without a less malignant precursor lesion and for which EGFR amplification is a characteristic genetic change. The p16 protein was not detectable in 15 of 22 glioblastomas but only 4 of these showed homozygous deletion of the gene. The alternative transcript p16 beta, for which a growth-suppressing function has been suggested, was co-expressed with p16 alpha mRNA in most cases. Hypermethylation of CpG islands in the 5' region of the p16 gene was identified in only 1 case, suggesting that this alternative mechanism of gene silencing is rarely responsible for loss of p16 expression in glioblastomas. Likewise, only 1 glioblastoma carried a p16 mutation and in addition, unexpectedly, a homozygous deletion of p16 in approximately 80% of tumor cells. This mutation, Arg24Pro, has previously been identified in a melanoma kindred.
Mots-clé
Adolescent Adult Aged Aged, 80 and over Cyclin D1/genetics Cyclin-Dependent Kinase Inhibitor p16/analysis/*genetics DNA Methylation Female *Gene Deletion Glioblastoma/*genetics Humans Male Middle Aged Mutation *Polymerase Chain Reaction RNA, Messenger/analysis Receptor, Epidermal Growth Factor/*genetics
Pubmed
Web of science
Création de la notice
25/01/2008 13:06
Dernière modification de la notice
20/08/2019 15:51
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