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Molecular Analysis of the PTEN, TP53 and CDKN2A Tumor Suppressor Genes in Long-term Survivors of Glioblastoma Multiforme

Authors
  • Kraus, Jürgen A.1
  • Glesmann, Nicole1
  • Beck, Martina1
  • Krex, Dietmar2
  • Klockgether, Thomas1
  • Schackert, Gabriele2
  • Schlegel, Uwe1
  • 1 University of Bonn Medical Center, Department of Neurology, Bonn, Germany , Bonn
  • 2 University of Dresden, Department of Neurosurgery, Dresden, Germany , Dresden
Type
Published Article
Journal
Journal of Neuro-Oncology
Publisher
Springer-Verlag
Publication Date
Jun 01, 2000
Volume
48
Issue
2
Pages
89–94
Identifiers
DOI: 10.1023/A:1006402614838
Source
Springer Nature
Keywords
License
Yellow

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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