Aberrant Hypermethylation of Non-Promoter Zygote Arrest 1 (Zar1) in Human Brain Tumors
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概要
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Zygote arrest 1 (ZAR1) is a novel maternal-effect gene which is extremely important during the oocyte-to-embryo transition. Comprehensive methylation analysis of tumor-specific differentially methylated regions in human malignant melanoma has recently led to the identification of non-promoter hypermethylation of the ZAR1 gene that had never been previously linked to aberrant methylation. Strikingly, 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. The present study searched for non-promoter ZAR1 hypermethylation in 90 primary human brain tumor samples, normal brain tissue from one autopsy case, and 7 glioma cell lines, employing Sequenom MassARRAY, in which bisulfite-treated fragments are quantitatively detected using time-of-flight mass spectroscopy. ZAR1 transcript expression levels were also evaluated by quantitative real-time reverse transcription-polymerase chain reaction in the 7 glioma cell lines. Hypermethylation of ZAR1 was frequently found in diffuse astrocytomas (7/7, 100%), anaplastic astrocytomas (16/17, 94%), glioblastomas (27/29, 93%), oligodendrogliomas (3/3, 100%), anaplastic oligodendrogliomas (3/3, 100%), and pituitary adenomas (9/10, 90%), but not in pilocytic astrocytomas (0/3). Other tumor types showed infrequent ZAR1 hypermethylation: 1 (17%) of 6 vestibular schwannomas and 4 (33%) of 12 meningothelial meningiomas. The normal brain tissue revealed no evidence of ZAR1 methylation. All 7 glioma cell lines displayed aberrant hypermethylation of ZAR1, but none had detectable ZAR1 transcript. Our findings indicate that non-promoter hypermethylation of ZAR1 is extremely frequent in diffuse gliomas and pituitary adenomas, but methylation-related aberrant ZAR1 expression is far less likely to be related to glioma tumorigenesis.
- 社団法人 日本脳神経外科学会の論文
- 2010-12-15
著者
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WATANABE Takao
Department of Environmental Health, Miyagi University of Education
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KATAYAMA Yoichi
Department of Neurological Surgery, Nihon University School of Medicine
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OHTA Takashi
Department of Neurological Surgery, Nihon University School of Medicine
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YOSHINO Atsuo
Department of Neurological Surgery, Nihon University School of Medicine
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FUKUSHIMA Takao
Department of Neurological Surgery, Nihon University School of Medicine
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Yoshino Atsuo
Department Of Neurological Surgery Nihon University School Of Medicine
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YACHI Kazunari
Department of Neurological Surgery, Nihon University School of Medicine
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SHINOJIMA Yui
Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medi
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Fukushima Takao
Department Of Neurological Surgery Nihon University School Of Medicine
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Katayama Yoichi
Department Of Neurological Surgery Nihon University School Of Medicine
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Katayama Yoichi
Division Of Neurosurgery Department Of Neurological Surgery Nihon University School Of Medicine
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Watanabe Takao
Division Of Neurosurgery Department Of Neurological Surgery Nihon University School Of Medicine
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Shinojima Yui
Division Of Cancer Genetics Department Of Advanced Medical Science Nihon University School Of Medici
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Yachi Kazunari
Department Of Neurological Surgery Nihon University School Of Medicine
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TERUI Tadashi
Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine
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NAGASE Hiroki
Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medi
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Nagase Hiroki
Division Of Cancer Genetics Department Of Advanced Medical Science Nihon University School Of Medici
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Ohta Takashi
Department Of Neurological Surgery Nihon University School Of Medicine
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Nagase Hiroki
Division Of Cancer Genetics Department Of Advanced Medical Research Center Nihon University School O
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Terui Tadashi
Division Of Cutaneous Science Department Of Dermatology Nihon University School Of Medicine
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Ohta Takashi
Department Of Internal Medicine School Of Medicine Tokai University
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Ohta Takashi
Department Of Anesthesiology Toda Chuo Sougou Hospital
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Watanabe Takao
Department Of Applied Biology Kyoto Institute Of Technology
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Watanabe Takao
Departmant Of Mathematics Faculty Of Science Osaka University
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Shinojima Yui
Division Of Cutaneous Science Department Of Dermatology Nihon University School Of Medicine
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Katayama Yoichi
Department of Neurlogical Surgery, School of Medicine, Nihon University, Tokyo, Japan
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