2011 Fiscal Year Final Research Report
Epigenetic regulations associated with biological and clinical relevancies in diffuse gliomas
| Project/Area Number |
21591883
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Nihon University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HUKUSHIMA Takao 日本大学, 医学部, 助教 (20350019)
YOSHINO Atsuo 日本大学, 医学部, 准教授 (50256848)
KATAYAMA Yoichi 日本大学, 医学部, 教授 (00125048)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 神経膠腫 / メチル化 / エピジェネティクス / MassARRAY / ZAR1 |
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| Research Abstract |
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.
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[Journal Article] Gene expression profoles predicting the response to IFN-s and a combination of temozolomide and IFN-s in malignant gliomas2011
Author(s)
Yoshino A, Tashiro S, Ogino A, Yachi K, Ohta T, Fukushima T, Watanabe T, Katayama Y, Okamoto Y, Sano E, Tsumoto K
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Journal Title
Int J Oncol
Volume: 39
Pages: 529-542
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[Journal Article] Gene expression profiling predicts response to temozolomide in malignant gliomas2010
Author(s)
Yoshino A, Ogino A, Yachi K, Ohta T, Fukushima T, Watanabe T, Katayama Y, Okamoto Y, Naruse N, Sano E, Tsumoto K
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Journal Title
Int J Oncol
Volume: 36
Pages: 1367-1377
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[Presentation] 膠芽腫に対するテモゾロミドとIFN-betaの相乗効果2011
Author(s)
吉野篤緒, 谷地一成, 太田隆, 荻野暁義, 福島崇夫, 渡邉学郎, 片山容一, 岡本豊, 田代晋也, 佐野恵美子, 津本浩平
Organizer
第29回日本脳腫瘍学会学術集会
Place of Presentation
下呂
Year and Date
20111100
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[Presentation] Gene expression profiling predicts response to temozolomide in malignant gliomas2010
Author(s)
Yoshino A, Ogino A, Yachi K, Ohta T, Fukushima T, Watanabe T, Katayama Y, Okamoto Y, Naruse N, Sano E, Tsumoto K
Organizer
The 9^<th> Meeting of the European Association of NeuroOncology
Place of Presentation
Masstricht, Nerderland
Year and Date
20100900
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[Presentation] Pleomorphic granular cell astrocytoma in the pineal gland2010
Author(s)
Ohta T, Yachi K, Ogino A, Yokoyama T, Fukushima T, Watanabe T, Yoshino A, Katayama Y, Honma T, Sugitani M
Organizer
The 9^<th> Meeting of the European Association of NeuroOncology
Place of Presentation
Masstricht, Nerderland
Year and Date
20100900
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