Epigenetic Silencing of the Protocadherin Family Member PCDH-g-A11 in Astrocytomas1

In a microarray-based methylation analysis of astro-cytomas [World Health Organization (WHO) grade II], we identified a CpG island within the first exon of the protocadherin-g subfamily A11 (PCDH-g-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. Hypermethyla-tion 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-g-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, tran-scription of PCDH-g-A11 was restored. In summary, we have identified PCDH-g-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