Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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Methylation Status of the O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Gene Promoter in World Health Organization Grade III Gliomas

  • Yang, Seung-Heon (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Kim, Yong-Hwy (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Kim, Jin-Wook (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Park, Chul-Kee (Department of Neurosurgery, Seoul National University College of Medicine) ;
  • Park, Sung-Hye (Department of Pathology, Seoul National University College of Medicine) ;
  • Jung, Hee-Won (Department of Neurosurgery, Seoul National University College of Medicine)
  • Published : 2009.10.28
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Abstract

Objective : We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter in World Health Organization (WHO) grade III gliomas in association with other molecular markers to evaluate their prevalence. Methods : The samples of a total of 36 newly WHO grade III glioma patients including 19 anaplastic oligodendrogliomas (AO), 7 anaplastic oligoastrocytomas (AOA), and 10 anaplastic astrocytomas (AA) were analyzed. The methylation status of the MGMT gene promoter was confirmed by methylation-specific polymerase chain reaction. The 1p/19q chromosomal deletion status and EGFR amplification were assessed by Fluorescence In-Situ Hybridization. MGMT, EGFR, EGFRvlll, and p53 expression were analyzed by immunohistochemical staining. Results : The MGMT gene promoter was methylated in 32 (88.9%) and unmethylated in 4 (11.2%) Among them, all of the AO and AOA had methylated MGMT gene promoter without exception. Significant associations between MGMT gene promoter hypermethylation and 1p/19q deletion was observed (p=0.003). Other molecular markers failed to show significant associations between MGMT gene promoter statuses. Conclusion : There was extensive epigenetic silencing of MGMT gene in high grade gliomas with oligodendroglial component. Together with frequent 1p/19q co-deletion in oligodendroglial tumors, this may add plausible explanations supporting the relative favorable prognosis in oligodendroglial tumors compared with pure astrocytic tumors.

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References

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