Browse > Article
http://dx.doi.org/10.3340/jkns.2009.46.4.385

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)
Publication Information
Journal of Korean Neurosurgical Society / v.46, no.4, 2009 , pp. 385-388 More about this Journal
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.
Keywords
MGMT gene promoter; Methylation; 1p/19q; Oligodendroglioma; Methylation-specific PCR;
Citations & Related Records

Times Cited By Web Of Science : 5  (Related Records In Web of Science)
Times Cited By SCOPUS : 5
연도 인용수 순위
1 Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, et al. : Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343 : 1350-1354, 2000   DOI   ScienceOn
2 Jeon YK, Park K, Park CK, Paek SH, Jung HW, Park SH : Chromosome 1p and 19q status and p53 and p16 expression patterns as prognostic indicators of oligodendroglial tumors : a clinicopathological study using fluorescence in situ hybridization. Neuropathology 27 : 10-20, 2007   DOI   ScienceOn
3 Kleihues P, Burger PC, Scheithauer BW : The new WHO classification of brain tumours. Brain Pathol 3 : 255-268, 1993   DOI   ScienceOn
4 Lavon I, Zrihan D, Zelikovitch B, Fellig Y, Fuchs D, Soffer D, et al. : Longitudinal assessment of genetic and epigenetic markers in oligodendrogliomas. Clin Cancer Res 13 : 1429-1437, 2007   DOI   ScienceOn
5 M$\ddot{o}$llemann M, Wolter M, Felsberg J, Collins VP, Reifenberger G : Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors. Int J Cancer 113 : 379-385, 2005   DOI   ScienceOn
6 Pegg AE : Mammalian O6-alkylguanine-DNA alkyltransferase : regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res 50 : 6119-6129, 1990   ScienceOn
7 van den Bent MJ, Kros JM : Predictive and prognostic markers in neuro-oncology. J Neuropathol Exp Neurol 66 : 1074-1081, 2007   DOI   ScienceOn
8 Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG : Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59 : 793-797, 1999   ScienceOn
9 Dong SM, Pang JC, Poon WS, Hu J, To KF, Chang AR, et al. : Concurrent hypermethylation of multiple genes is associated with grade of oligodendroglial tumors. J Neuropathol Exp Neurol 60 : 808-816, 2001   ScienceOn
10 Nutt CL, Noble M, Chambers AF, Cairncross JG : Differential expression of drug resistance genes and chemosensitivity in glial cell lineages correlate with differential response of oligodendrogliomas and astrocytomas to chemotherapy. Cancer Res 60 : 4812-4818, 2000   ScienceOn
11 Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. : The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61 : 215-225; discussion 226-229, 2002   ScienceOn
12 Kuo LT, Kuo KT, Lee MJ, Wei CC, Scaravilli F, Tsai JC, et al. : Correlation among pathology, genetic and epigenetic profiles, and clinical outcome in oligodendroglial tumors. Int J Cancer 124 : 2872-2879, 2009   DOI   ScienceOn
13 Scheithauer BW, Fuller GN, VandenBerg SR : The 2007 WHO classification of tumors of the nervous system : controversies in surgical neuropathology. Brain Pathol 18 : 307-316, 2008   DOI   ScienceOn
14 Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. : The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114 : 97-109, 2007   DOI   ScienceOn
15 Alonso ME, Bello MJ, Gonzalez-Gomez P, Arjona D, Lomas J, de Campos JM, et al. : Aberrant promoter methylation of multiple genes in oligodendrogliomas and ependymomas. Cancer Genet Cytogenet 144 : 134-142, 2003   DOI   ScienceOn
16 Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. : MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352 : 997-1003, 2005   DOI   ScienceOn
17 Balana C, Ramirez JL, Taron M, Roussos Y, Ariza A, Ballester R, et al. : O6-methyl-guanine-DNA methyltransferase methylation in serum and tumor DNA predicts response to 1,3-bis(2-chloroethyl)-1-nitrosourea but not to temozolamide plus cisplatin in glioblastoma multiforme. Clin Cancer Res 9 : 1461-1468, 2003   ScienceOn
18 Paz MF, Yaya-Tur R, Rojas-Marcos I, Reynes G, Pollan M, Aguirre-Cruz L, et al. : CpG island hypermethylation of the DNA repair enzyme methyltransferase predicts response to temozolomide in primary gliomas. Clin Cancer Res 10 : 4933-4938, 2004   DOI   ScienceOn