title: Non-promoter hypermethylation of zygote arrest 1 (ZAR1) in human brain tumors.
abstract: Zygote arrest 1 (ZAR1) is a novel maternal-effect gene of crucial importance during the oocyte-to-embryo transition. Comprehensive methylation analysis of tumor-specific differently 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 in pilocytic astrocytomas. For other tumor types ZAR1 hypermethylation was infrequent: 17% of vestibular schwannomas and 33% of meningothelial meningiomas. Detectable ZAR1 transcript was not found in any of hypermethylated glioma cell lines. Our results 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.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. takao@med.nihon-u.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yachi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohta
authors.forename: Takao
authors.initials: T
authors.lastname: Fukushima
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yoshino
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
authors.forename: Yui
authors.initials: Y
authors.lastname: Shinojima
authors.forename: Tadashi
authors.initials: T
authors.lastname: Terui
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism; D004527:Egg Proteins / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009865:Oocytes / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D015053:Zygote / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004527:Egg Proteins; C471631:Zar1 protein, human