Isocitrate Dehydrogenase Mutations are Better Prognostic Marker than O6-methylguanine-DNA Methyltransferase Promoter Methylation in Glioblastomas – a Retrospective, Single-centre Molecular Genetics Study of Gliomas

2017 ◽  
Vol 30 (5) ◽  
pp. 361-371 ◽  
Author(s):  
Magdalena Houdová Megeova ◽  
Jiri Drabek ◽  
Zachary Dwight ◽  
Radek Trojanec ◽  
Vladimira Koudelakova ◽  
...  
Keyword(s):  
Molecular Genetics ◽  
Prognostic Marker ◽  
Promoter Methylation ◽  
Isocitrate Dehydrogenase ◽  
Dna Methyltransferase ◽  
Single Centre ◽  
Methylguanine Dna Methyltransferase

scholarly journals Implications of MGMT promoter methylation and its downstream hMSH2 mRNA in primary malignant glioma

2019 ◽  
Author(s):  
Jeru-Manoj Manuel ◽  
K V L Narasinga Rao ◽  
G K Chetan
Keyword(s):  
Treatment Response ◽  
Prognostic Marker ◽  
Promoter Methylation ◽  
Dna Methyltransferase ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Primary Component ◽  
Over Expression ◽  
Methylguanine Dna Methyltransferase ◽  
Protein Dimer

AbstractBackgroundHypermethylation of 06-methylguanine DNA methyltransferase (MGMT)promoter seen in high grade gliomas (HGG) leads to the accumulation of O6-meG DNA damage which mispairs with thymine, requiring recognition by mismatch repair protein dimer MutSα, whose primary component is coded by Human MutS homolog protein 2 (hMSH2). O6-meG repair necessitates the interaction/combined action of MGMT andhMSH2 to maintain genomic stability. Analysis of the correlation between MGMT methylation and hMSH2mRNAexpression in HGG and their role in the prognosis was explored.MethodsStudy was performed on 54 primary-frontal lobe HGG tumors, MGMT promoter methylation was detected by Q-MSP and Q-PCR was used to analyse hMSH2 m-RNA expression levels.ResultsMGMT methylation was seen in 62%patients the mean percentage of methylation (PoM) being (17.62±17.20) %. MGMT PoM≥10% had improved Progression free survival (p=0.015) and ≥8% had better Overall survival (p=0.043), indicating its predictive significance. Over expression of hMSH2 was seen in 50% patients with a median fold change of 2.74 (p=0.021). Univariate analysis of high hMSH2 expression with therapy(CT+RT) showed poor PFS (p=0.002). There was no correlation between MGMT methylation and hMSH2 expression.ConclusionMGMT PoM of ≥10% is a significant prognostic marker. Over expression of hMSH2 is prognostic marker for poor treatment response. Lack of/aberrant correlation between MGMT andhMSH2 could indicate impaired DNA repair of O6-meG in HGG, and this could be one of the factors responsible for both, gliomagenesis and variations in treatment response.

scholarly journals Alteration in the expression of MGMT and RUNX3 due to non-CpG promoter methylation and their correlation with different risk factors in esophageal cancer patients

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770163 ◽  
Author(s):  
Snigdha Saikia ◽  
Asad Ur Rehman ◽  
Prajjalendra Barooah ◽  
Preeti Sarmah ◽  
Mallika Bhattacharyya ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Transcription Factor ◽  
Promoter Methylation ◽  
Messenger Rna ◽  
Dna Methyltransferase ◽  
Rna Expression ◽  
Betel Nut ◽  
Methylguanine Dna Methyltransferase ◽  
Related Transcription Factor ◽  
Transcription Factor 3

Promoter methylation reflects in the inactivation of different genes like O6-methylguanine-DNA methyltransferase DNA repair gene and runt-related transcription factor 3, a known tumor suppressor gene in various cancers such as esophageal cancer. The promoter methylation was evaluated for O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in CpG, CHH, and CHG context (where H is A, T, or C) by next-generation sequencing. The methylation status was correlated with quantitative messenger RNA expression. In addition, messenger RNA expression was correlated with different risk factors like tobacco, alcohol, betel nut consumption, and smoking habit. CpG methylation of O6-methylguanine-DNA methyltransferase promoter had a positive association in the development of esophageal cancer (p < 0.05), whereas runt-related transcription factor 3 promoter methylation showed no significant association (p = 1.0) to develop esophageal cancer. However, the non-CpG methylation, CHH, and CHG were significantly correlated with O6-methylguanine-DNA methyltransferase (p < 0.05) and runt-related transcription factor 3 (p < 0.05) promoters in the development of esophageal cancer. The number of cytosine converted to thymine (C→T) in O6-methylguanine-DNA methyltransferase promoter showed a significant correlation between cases and controls (p < 0.05), but in runt-related transcription factor 3 no such significant correlation was observed. Besides, messenger RNA expression was found to be significantly correlated with promoter hypermethylation of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 in the context of CHG and CHH (p < 0.05). The CpG hypermethylation in O6-methylguanine-DNA methyltransferase showed positive (p < 0.05) association, whereas in runt-related transcription factor 3, it showed contrasting negative association (p = 0.23) with their messenger RNA expression. Tobacco, betel nut consumption, and smoking habits were associated with altered messenger RNA expression of O6-methylguanine-DNA methyltransferase (p < 0.05) and betel nut consumption and smoking habits were associated with runt-related transcription factor 3 (p < 0.05). There was no significant association between messenger RNA expression of O6-methylguanine-DNA methyltransferase and runt-related transcription factor 3 with alcohol consumption (p = 0.32 and p = 0.15). In conclusion, our results suggest that an aberrant messenger RNA expression may be the outcome of CpG, CHG, and CHH methylation in O6-methylguanine-DNA methyltransferase, whereas outcome of CHG and CHH methylation in runt-related transcription factor 3 promoters along with risk factors such as consumption of tobacco, betel nut, and smoking habits in esophageal cancer from Northeast India.

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