The Significance of MGMT Promoter Methylation Status in Diffuse Glioma

被引:4
作者
Jovanovic, Nikola [1 ]
Lazarevic, Milica [1 ]
Cvetkovic, Vladimir J. [1 ]
Nikolov, Vesna [2 ]
Peric, Jelena Kostic [3 ]
Ugrin, Milena [3 ]
Pavlovic, Sonja [3 ]
Mitrovic, Tatjana [1 ]
机构
[1] Univ Nis, Fac Sci & Math, Dept Biol & Ecol, Lab Mol Biol & Biotechnol, Nish 18000, Serbia
[2] Univ Nis, Fac Med, Clin Neurosurg, Ctr Clin, Nish 18000, Serbia
[3] Univ Belgrade, Inst Mol Genet & Genet Engn, Lab Mol Biomed, Belgrade 11042, Serbia
关键词
diffuse glioma; glioblastoma; MGMT; IDH1; IDH2; MSP; qMSP; CENTRAL-NERVOUS-SYSTEM; NEWLY-DIAGNOSED GLIOBLASTOMA; INTEGRATED GENOMIC ANALYSIS; IDH1; MUTATIONS; PROGNOSTIC-FACTORS; TEMOZOLOMIDE CHEMOTHERAPY; ADJUVANT TEMOZOLOMIDE; PREDICTS SURVIVAL; METHYLTRANSFERASE; RADIOTHERAPY;
D O I
10.3390/ijms232113034
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A single-institution observational study with 43 newly diagnosed diffuse gliomas defined the isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation status and evaluated the prognostic relevance of the methylation status of the epigenetic marker O-6-methylguanine-DNA methyltransferase (MGMT). Younger patients (<50 years) with surgically resected glioma and temozolomide (TMZ) adjuvant chemotherapy were associated with better prognosis, consistent with other studies. The methylation status depends on the chosen method and the cut-off value determination. Methylation-specific PCR (MSP) established the methylation status for 36 glioma patients (19 (52.8%) positively methylated and 17 (47.2%) unmethylated) without relevancy for the overall survival (OS) (p = 0.33). On the other side, real-time methylation-specific PCR (qMSP) revealed 23 tumor samples (54%) that were positively methylated without association with OS (p = 0.15). A combined MSP analysis, which included the homogenous cohort of 24 patients (>50 years with surgical resection and IDH1/2-wildtype diffuse glioma), distinguished 10 (41.6%) methylated samples from 14 (58.4%) unmethylated samples. Finally, significant correlation between OS and methylation status was noticed (p approximate to 0.05). The OS of the hypermethylated group was 9.6 +/- 1.77 months, whereas the OS of the unmethylated group was 5.43 +/- 1.04 months. Our study recognized the MGMT promoter methylation status as a positive prognostic factor within the described homogenous cohort, although further verification in a larger population of diffuse gliomas is required.
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页数:20
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