Artikel
The comparison between focal and total DNA methylation in gliomas
Der Vergleich zwischen fokaler und totaler DNA-Methylierung bei Gliome
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Autoren
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Aleksandra Majchrzak-Celińska
- Karol Marcinkowski University of Medical Sciences, Pharmaceutical Biochemistry, Poznan, Polen
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Mirosława Naskręt-Barciszewska
- Polish Academy of Sciences, Institute of Bioorganic Chemistry, Poznan, Polen
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Witold Nowak
- Adam Mickiewicz University, Molecular Biology Techniques Laboratory, Poznan, Polen
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Paulina Śron
- Karol Marcinkowski University of Medical Sciences, Pharmaceutical Biochemistry, Poznan, Polen
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Anna-Maria Barciszewska
- Indywidualna Praktyka Lekarska Anna-Maria Barciszewska, Skorzewo, Polen; Heliodor Swiecicki Clinical Hospital in Poznan, Department of Neurosurgery and Neurotraumatology, Poznan, Polen; Karol Marcinkowski University of Medical Sciences, Neurosurgery and Neurotraumatology, Poznan, Polen
| Veröffentlicht: | 25. Mai 2022 |
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Gliederung
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Objective: The role of epigenetic mechanisms in gliomagenesis is undoubtful. However, their influence on specific pathological pathways is not clear. Previously we have shown that loss in total DNA methylation (m5C contents) correlates with tumor malignancy as well as with oxidative DNA damage. It has also been shown that promoter methylation of many genes is important for gliomas’ malignancy and predictive for the treatment outcome. In carcinogenesis global DNA hypomethylation, as well as hypermethylation of specific genes can be observed. The aim of our project was to evaluate the correlation between total DNA methylation level and promoter methylation of selected genes.
Methods: We analysed DNA of glioma tissues from 60 patients. For total DNA methylation analysis we used the postlabelling method with 32 phosphate. Specific promoter methylation analysis was done for MGMT (O-6-Methylguanine-DNA Methyltransferase), MPG (DNA-3-methyladenine glycosylase), and GJA1 (Gap junction alpha-1 protein / connexin 43), with the methylation-sensitive high-resolution melting (MS-HRM) method.
Results: Total DNA methylation was reversely correlated with brain tumor grade, showing that 5-methylcytosine loss is important step in gliomagenesis. From analysed 3 genes only MPG promoter methylation showed clear low reverse correlation with tumor grade. Promoter methylation in GJA1 show low correlation with both, MGMT and MPG, but there was no relation between MGMT and MPG. IDHwt presence was significantly correlated with higher tumor grade, but promoter methylation of MPG and GJA1 were better correlated with IDH status than in MGMT.
Conclusion: We have found a clear correlation between total DNA methylation and tumor malignancy. Promoter methylation correlates with tumor grade only in MPG case, and is not highly correlated with total DNA methylation showing low significance in selected cases. Therefore one can suggest diverse mechanisms controlling global and focal DNA methylation changes. It also shows that total DNA methylation is simple, and effective predictor of tumor grade.
