Epigenetic silencing of the protocadherin family member PCDH-gamma-A11 in astrocytomas.
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| 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.
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| Authors | Anke Waha, Stefanie Güntner, Tim Hui-Ming Huang, Pearlly S Yan, Bülent Arslan, Torsten Pietsch, Otmar D Wiestler, Andreas Waha |
| Journal | Neoplasia (New York, N.Y.) (Neoplasia) Vol. 7 Issue 3 Pg. 193-9 (Mar 2005) ISSN: 1522-8002 [Print] United States |
| PMID | 15799819 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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