Prognostic significance of MGMT promoter methylation in diffuse glioma patients

被引:6
作者
Jovanovic, Nikola [1 ]
Mitrovic, Tatjana [1 ]
Cvetkovic, Vladimir J. [1 ]
Tosic, Svetlana [1 ]
Vitorovic, Jelena [1 ]
Stamenkovic, Slavisa [1 ]
Nikolov, Vesna [2 ]
Kostic, Aleksandar [2 ]
Vidovic, Natasa [3 ]
Jevtovic-Stoimenov, Tatjana [4 ]
Pavlovic, Dusica [4 ]
机构
[1] Univ Nis, Fac Sci & Math, Dept Biol & Ecol, Visegradska 33, Nish 18000, Serbia
[2] Univ Nis, Fac Med, Clin Ctr, Clin Neurosurg, Nish, Serbia
[3] Univ Nis, Fac Med, Pathol & Pathol Anat Ctr, Nish, Serbia
[4] Univ Nis, Fac Med, Inst Biochem, Nish, Serbia
关键词
Diffuse glioma; MGMT; overall survival; CpG; prognosis; MSP; DNA METHYLATION; GLIOBLASTOMA; HYPERMETHYLATION; TEMOZOLOMIDE; MECHANISMS; MUTATIONS; SURVIVAL; BRAIN; AGE;
D O I
10.1080/13102818.2019.1604158
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Current treatment options for diffuse glioma patients include maximum safe resection followed by a combination of radiation therapy and chemotherapy with alkylating agents. The DNA-repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT) counteracts the cytotoxic effect of alkylating agents and mediates chemoresistance. Disruption of the DNA methylation mechanism in diffuse glioma cells results in epigenetic silencing of MGMT through methylation of cytidine-phosphate-guanosine dinucleotides (CpG) in the promoter region. The methylation status of MGMT is widely accepted to be a strong prognostic factor in diffuse glioma patients. This study was designed to screen Serbian diffuse glioma patients for hypermethylation of the MGMT promoter and to estimate its impact on overall survival. The results obtained in our study on 33 samples of diffuse glioma detected a positive methylation status in 17 patients (51.5%) by methylation-specific polymerase chain reaction. The positive methylation status of the MGMT promoter did not correlate with overall survival. In this study group, the patients older than 50 years had significantly lower overall survival in comparison with younger patients (7 months-19 months median survival). Extent of tumour resection also had influence on overall survival of patients. The relevance of the MGMT promoter methylation status should be further evaluated in a larger study and in association with other markers.
引用
收藏
页码:639 / 644
页数:6
相关论文
共 30 条
[21]  
Nikolov V, 2018, J BUON, V23, P173
[22]  
Puduvalli Vinay K, 2017, Am Soc Clin Oncol Educ Book, V37, P175, DOI 10.14694/EDBK_175003
[23]   Mechanisms of chemoresistance to alkylating agents in malignant glioma [J].
Sarkaria, Jann N. ;
Kitange, Gaspar J. ;
James, C. David ;
Plummer, Ruth ;
Calvert, Hilary ;
Weller, Michael ;
Wick, Wolfgang .
CLINICAL CANCER RESEARCH, 2008, 14 (10) :2900-2908
[24]   Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma [J].
Stupp, R ;
Mason, WP ;
van den Bent, MJ ;
Weller, M ;
Fisher, B ;
Taphoorn, MJB ;
Belanger, K ;
Brandes, AA ;
Marosi, C ;
Bogdahn, U ;
Curschmann, J ;
Janzer, RC ;
Ludwin, SK ;
Gorlia, T ;
Allgeier, A ;
Lacombe, D ;
Cairncross, JG ;
Eisenhauer, E ;
Mirimanoff, RO ;
Van Den Weyngaert, D ;
Kaendler, S ;
Krauseneck, P ;
Vinolas, N ;
Villa, S ;
Wurm, RE ;
Maillot, MHB ;
Spagnolli, F ;
Kantor, G ;
Malhaire, JP ;
Renard, L ;
De Witte, O ;
Scandolaro, L ;
Vecht, CJ ;
Maingon, P ;
Lutterbach, J ;
Kobierska, A ;
Bolla, M ;
Souchon, R ;
Mitine, C ;
Tzuk-Shina, T ;
Kuten, A ;
Haferkamp, G ;
de Greve, J ;
Priou, F ;
Menten, J ;
Rutten, I ;
Clavere, P ;
Malmstrom, A ;
Jancar, B ;
Newlands, E .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (10) :987-996
[25]   Epidemiologic and Molecular Prognostic Review of Glioblastoma [J].
Thakkar, Jigisha P. ;
Dolecek, Therese A. ;
Horbinski, Craig ;
Ostrom, Quinn T. ;
Lightner, Donita D. ;
Barnholtz-Sloan, Jill S. ;
Villano, John L. .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2014, 23 (10) :1985-1996
[26]   Effect of pretreatment clinical factors on overall survival in glioblastoma multiforme: a Surveillance Epidemiology and End Results (SEER) population analysis [J].
Thumma, Sudheer R. ;
Fairbanks, Robert K. ;
Lamoreaux, Wayne T. ;
Mackay, Alexander R. ;
Demakas, John J. ;
Cooke, Barton S. ;
Elaimy, Ameer L. ;
Hanson, Peter W. ;
Lee, Christopher M. .
WORLD JOURNAL OF SURGICAL ONCOLOGY, 2012, 10
[27]   The Challenges and the Promise of Molecular Targeted Therapy in Malignant Gliomas [J].
Wang, Hongxiang ;
Xu, Tao ;
Jiang, Ying ;
Xu, Hanchong ;
Yan, Yong ;
Fu, Da ;
Chen, Juxiang .
NEOPLASIA, 2015, 17 (03) :239-255
[28]  
Wesseling P., 2011, Diagnostic Histopathol, V17, P486, DOI [10.1016/j.mpdhp.2011.08.005, DOI 10.1016/J.MPDHP.2011.08.005]
[29]   Association of DNA methylation in the brain with age in older persons is confounded by common neuropathologies [J].
Yang, Jingyun ;
Yu, Lei ;
Gaiteri, Christopher ;
Srivastava, Gyan P. ;
Chibnik, Lori B. ;
Leurgans, Sue E. ;
Schneider, Julie A. ;
Meissner, Alexander ;
De Jager, Philip L. ;
Bennett, David A. .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2015, 67 :58-64
[30]   Common Polymorphisms in the MDM2 and TP53 Genes and the Relationship between TP53 Mutations and Patient Outcomes in Glioblastomas [J].
Zawlik, Izabela ;
Kita, Daisuke ;
Vaccarella, Salvatore ;
Mittelbronn, Michel ;
Franceschi, Silvia ;
Ohgaki, Hiroko .
BRAIN PATHOLOGY, 2009, 19 (02) :188-194