Acta Neuropathologica

, Volume 106, Issue 5, pp 479–485

PTEN methylation and expression in glioblastomas

  • Nathalie Baeza
  • Michael Weller
  • Yasuhiro Yonekawa
  • Paul Kleihues
  • Hiroko Ohgaki
Regular Paper

DOI: 10.1007/s00401-003-0748-4

Cite this article as:
Baeza, N., Weller, M., Yonekawa, Y. et al. Acta Neuropathol (2003) 106: 479. doi:10.1007/s00401-003-0748-4

Abstract

The tumor suppressor gene PTEN on chromosome 10q23.3 regulates the Akt signaling pathway and modulates cell growth and apoptosis. The PTEN gene is mutated in 20–40% of glioblastomas. In this study, we assessed whether loss of PTEN expression is also caused epigenetically. Methylation-specific PCR revealed that CpG islands of the PTEN promoter were methylated in 27 of 77 (35%) glioblastomas and in 4 of 11 (36%) glioblastoma cell lines. Only two glioblastomas showed loss of PTEN immunoreactivity in the entire biopsy; both had a missense PTEN mutation and LOH at the PTEN locus, but lacked PTEN methylation. In biopsy specimens with focal loss of PTEN expression, DNA samples extracted from microdissected foci showed PTEN methylation only in areas with loss of PTEN expression. These results suggest that PTEN methylation occurs frequently in glioblastomas and may be associated with focal loss of PTEN expression. However, the correlation between PTEN methylation, PTEN mutations, LOH at the PTEN locus, and loss of PTEN protein expression was inconsistent. Possible reasons for discrepancies between gene status and protein expression include differences in the biological effect of specific PTEN mutations and the possibility that the processed PTEN pseudogene on 9p21 is expressed in glioblastomas and co-reacts with the PTEN antibody.

Keywords

PTEN Glioblastoma Promoter methylation LOH on chromosome 10 PTEN pseudogene 

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Nathalie Baeza
    • 1
  • Michael Weller
    • 2
  • Yasuhiro Yonekawa
    • 3
  • Paul Kleihues
    • 1
  • Hiroko Ohgaki
    • 1
  1. 1.International Agency for Research on Cancer (IARC)LyonFrance
  2. 2.Laboratory of Molecular Neuro-Oncology, Department of NeurologyUniversity of TübingenTübingenGermany
  3. 3.Department of NeurosurgeryUniversity Hospital ZürichZürichSwitzerland

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