Epigenetic silencing of the protocadherin family member PCDH-γ-A11 in astrocytomas

Anke Waha, Stefanie Güntner, Tim Hui Ming Huang, Pearlly S. Yan, Bülent Arslan, Torsten Pietsch, Otmar D. Wiestler, Andreas Waha

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

In a microarray-based methylation analysis of astrocytomas [World Health Organization (WHO) grade II], we identified a CpG island within the first exon of the protocadherin-γ subfamily A11 (PCDH-γ-A11) gene that showed hypermethylation compared to normal brain tissue. Bisulfite sequencing and combined bisulfite restriction analysis (COBRA) was performed to screen low- and high-grade astrocytomas for the methylation status of this CpG island. Hypermethylation was detected in 30 of 34 (88%) astrocytomas (WHO grades II and III), 20 of 23 (87%) glioblastomas (WHO grade IV), and 8 of 8 (100%) glioma cell lines. There was a highly significant correlation (P = .00028) between PCDH-γ-A11 hypermethylation and decreased transcription as determined by competitive reverse transcription polymerase chain reaction in WHO grades II and III astrocytomas. After treatment of glioma cell lines with a demethylating agent, transcription of PCDH-γ-A11 was restored. In summary, we have identified PCDH-γ-A11 as a new target silenced epigenetically in astrocytic gliomas. The inactivation of this cell-cell contact molecule might be involved in the invasive growth of astrocytoma cells into normal brain parenchyma.

Original languageEnglish (US)
Pages (from-to)193-199
Number of pages7
JournalNeoplasia
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 2005

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Keywords

  • Expression
  • Glioma
  • Methylation
  • PCDH-γ-A11
  • cRT-PCR

ASJC Scopus subject areas

  • Cancer Research

Cite this

Waha, A., Güntner, S., Huang, T. H. M., Yan, P. S., Arslan, B., Pietsch, T., ... Waha, A. (2005). Epigenetic silencing of the protocadherin family member PCDH-γ-A11 in astrocytomas. Neoplasia, 7(3), 193-199. https://doi.org/10.1593/neo.04490