Aberrant promoter methylation and expression of the imprinted PEG3 gene in glioma

• Published in: Proceedings of the Japan Academy, Series B Vol. 85; no. 4; pp. 157 - 165
• Main Authors: OTSUKA, Susumu, MAEGAWA, Shinji, TAKAMURA, Ayumi, KAMITANI, Hideki, WATANABE, Takashi, OSHIMURA, Mitsuo, NANBA, Eiji
• Format: Journal Article
• Language: English
• Published: Japan The Japan Academy 2009
• Subjects: Adolescent; Adult; Aged; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Child; Child, Preschool; CpG Islands; DNA methylation; DNA Methylation - genetics; DNA Methylation - physiology; Epigenesis, Genetic; epigenetic silencing; Female; Gene Expression Regulation, Neoplastic; Genomic Imprinting; glioma; Glioma - genetics; Glioma - metabolism; Humans; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Male; Middle Aged; PEG3; Polymorphism, Genetic; Promoter Regions, Genetic; Young Adult
• ISSN: 0386-2208; 1349-2896
• DOI: 10.2183/pjab.85.157

Glioma includes astrocytoma, oligodendroglioma, ependymoma and glioblastoma. We previously reported the epigenetic silencing of paternally expressed gene 3 (PEG3) in glioma cell lines. In this study, we investigated methylation of an exonic CpG island in the promoter region and the expression of PEG3 gene in 20 glioma and 5 non-tumor tissue samples. We found wide variations in the methylation level. Hypomethylaiton and hypermethylation was found in 3 and 4 glioma tissue samples, respectively. Monoallelic expression, which is an evidence of an imprinted gene, was maintained in eight out of nine informative cases which have T/C polymorphisms in PEG3. The lower gene expression, which suggested epigenetic silencing of PEG3, was confirmed statistically in glioblastoma using quantitative reverse-transcription polymerase chain reaction. Interestingly, we found higher expression of PEG3 in two out of three oligodendrogliomas. A negative correlation between the methylation level and gene expression was shown by regression analysis. These results suggest that the abnormal regulation of PEG3 is associated with several glioma subtypes and that it plays an important role in tumorigenesis. (Communicated by Takao SEKIYA, M.J.A.)