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

Neoplasia. 2005 Mar;7(3):193-9. doi: 10.1593/neo.04490.

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-gamma subfamily A11 (PCDH-gamma-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-gamma-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-gamma-A11 was restored. In summary, we have identified PCDH-gamma-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Astrocytoma / genetics*
  • Astrocytoma / metabolism
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Base Sequence
  • Brain / metabolism
  • Cadherins / genetics*
  • Cell Line, Tumor
  • CpG Islands
  • DNA Methylation
  • Decitabine
  • Exons
  • Gene Silencing*
  • Humans
  • Methylation
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfites / pharmacology
  • Transcription, Genetic

Substances

  • Cadherins
  • PCDH11X protein, human
  • Sulfites
  • Decitabine
  • Azacitidine