Epigenetic silencing of the protocadherin family member PCDH-gamma-A11 in astrocytomas.
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.
Waha
Anke
A
Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
Güntner
Stefanie
S
Huang
Tim Hui-Ming
TH
Yan
Pearlly S
PS
Arslan
Bülent
B
Pietsch
Torsten
T
Wiestler
Otmar D
OD
Waha
Andreas
A
D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D000077209:Decitabine; D005091:Exons; D020868:Gene Silencing; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D000091363:Protocadherins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013447:Sulfites / Q000494:pharmacology; D014158:Transcription, Genetic
D015820:Cadherins; C404498:PCDH11X protein, human; D000091363:Protocadherins; D013447:Sulfites; D000077209:Decitabine; D001374:Azacitidine