Epigenetic silencing of PEG3 gene expression in human glioma cell lines

Genomic imprinting, the phenomenon in which alleles of genes are expressed differentially depending on their parental origins, has important consequen ces for mammalian development, and disturbance of normal imprinting leads t o abnormal embryogenesis and some inherited diseases and is also associated with various cancers. In the context of screening for novel imprinted gene s on human chromosome 19q13.4 with mouse A9 hybrids, we identified a matern al allele-specific methylated CpG island in exon 1 of paternally expressed imprinted gene 3 (PEG3), a gene that exhibits paternal allele-specific expr ession. Because PEG3 expression is downregulated in some gliomas and glioma cell lines, despite high-level expression in normal brain tissues, we inve stigated whether the loss of PEG3 expression is related to epigenetic modif ications involving DNA methylation. We found monoallelic expression of PEG3 in all normal brain tissues examined and five of nine glioma cell lines th at had both unmethylated and methylated alleles; the remaining four glioma cell lines exhibited gain of imprinting with hypermethylated alleles. In ad dition, treatment of glioma cell lines with the DNA demethylating agent 5-a za-2 ' -deoxycytidine reversed the silencing of PEG3 biallelically. In this article, we report that the epigenetic silencing of PEG3 expression in gli oma cell lines depends on aberrant DNA methylation of an exonic CpG island, suggesting that PEG3 contributes to glioma carcinogenesis in certain cases . (C) 2001 Wiley-Liss, Inc.