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 journalArticlepeer-review

82 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
StatePublished - Mar 2005

Keywords

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

ASJC Scopus subject areas

  • Cancer Research

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