Epigenetic regulations associated with biological and clinical relevancies in diffuse gliomas

点击翻译按钮获取中文摘要

Zygote arrest 1(ZAR1) is a novel maternal-effect gene that plays crucial roles during the oocyte-to-embryo transition. Comprehensive methylation analysis of tumor-specific differentially methylated regions in human malignant melanomas has recently led to the identification of non-promoter hypermethylation of the ZAR1 gene that had never been identified as an aberrant methylated region in any human tumor. Notably, ZAR1 hypermethylation was frequently observed in melanomas but was absent in benign nevi, and ZAR1 expression was found to be up-regulated in methylated tumors. These findings prompted us to screen for ZAR1 non-promoter methylation in various types of human brain tumors using MassARRAY EpiTYPER. Strikingly, hypermethylation of ZAR1 was observed frequently in diffuse astrocytomas(100%), anaplastic astrocytomas(94%), glioblastomas(93%), oligodendrogliomas(100%), anaplastic oligodendrogliomas(100%), and pituitary adenomas(90%), but not at all pilocytic astrocytomas. Other tumor types showed infrequent ZAR1 hypermethylation : 17% of vestibular schwannomas and 33% of meningothelial meningiomas. Detectable ZAR1 transcript was not found in any of hypermethylated glioma cell lines. Our data indicate that hypermethylation of the ZAR1 non-promoter is extremely frequent in diffuse gliomas and pituitary adenomas, although ZAR1 expression is unlikely to play a tumorigenic role.