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Brain Tumor Pathology

, Volume 28, Issue 3, pp 199–202 | Cite as

Non-promoter hypermethylation of zygote arrest 1 (ZAR1) in human brain tumors

  • Takao WatanabeEmail author
  • Kazunari Yachi
  • Takashi Ohta
  • Takao Fukushima
  • Atsuo Yoshino
  • Yoichi Katayama
  • Yui Shinojima
  • Tadashi Terui
  • Hiroki Nagase
Review Article

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.

Keywords

Brain tumor Glioma Mass spectroscopy Methylation Zygote arrest 1 

Notes

Acknowledgments

This work was supported in part by Grants-in-Aids for Scientific Research from the Japan Society for the Promotion of Science (grant number 21591883) and the Academic Frontier Project of the 2006 Project for Private Universities, a matching fund subsidy from MEXT (to Hiroki Nagase).

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Copyright information

© The Japan Society of Brain Tumor Pathology 2011

Authors and Affiliations

  • Takao Watanabe
    • 1
    Email author
  • Kazunari Yachi
    • 1
  • Takashi Ohta
    • 1
  • Takao Fukushima
    • 1
  • Atsuo Yoshino
    • 1
  • Yoichi Katayama
    • 1
  • Yui Shinojima
    • 2
    • 3
  • Tadashi Terui
    • 3
  • Hiroki Nagase
    • 2
  1. 1.Department of Neurological SurgeryNihon University School of MedicineTokyoJapan
  2. 2.Division of Cancer Genetics, Department of Advanced Medical ScienceNihon University School of MedicineTokyoJapan
  3. 3.Division of Cutaneous Science, Department of DermatologyNihon University School of MedicineTokyoJapan

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