Methylation Status of the O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Gene Promoter in World Health Organization Grade III Gliomas |
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Authors: | Seung-Heon Yang Yong Hwy Kim Jin Wook Kim Chul-Kee Park Sung-Hye Park and Hee-Won Jung |
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Institution: | 1Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.;2Department of Pathology, Seoul National University College of Medicine, Seoul, Korea. |
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Abstract: | ObjectiveWe 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.MethodsThe 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, EGFRvIII, and p53 expression were analyzed by immunohistochemical staining.ResultsThe 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.ConclusionThere 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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Keywords: | MGMT gene promoter Methylation 1p/19q Oligodendroglioma Methylation-specific PCR |
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