Total DNA Methylation Changes Reflect Random Oxidative DNA Damage in Gliomas.
Anna-Maria BarciszewskaMałgorzata Giel-PietraszukPatrick M PerrigueMirosława Naskręt-BarciszewskaPublished in: Cells (2019)
DNA modifications can be used to monitor pathological processes. We have previously shown that estimating the amount of the main DNA epigenetic mark, 5-methylcytosine (m5C), is an efficient and reliable way to diagnose brain tumors, hypertension, and other diseases. Abnormal increases of reactive oxygen species (ROS) are a driving factor for mutations that lead to changes in m5C levels and cancer evolution. 8-oxo-deoxyguanosine (8-oxo-dG) is a specific marker of ROS-driven DNA-damage, and its accumulation makes m5C a hotspot for mutations. It is unknown how m5C and 8-oxo-dG correlate with the malignancy of gliomas. We analyzed the total contents of m5C and 8-oxo-dG in DNA from tumor tissue and peripheral blood samples from brain glioma patients. We found an opposite relationship in the amounts of m5C and 8-oxo-dG, which correlated with glioma grade in the way that low level of m5C and high level of 8-oxo-dG indicated increased glioma malignancy grade. Our results could be directly applied to patient monitoring and treatment protocols for gliomas, as well as bolster previous findings, suggesting that spontaneously generated ROS react with m5C. Because of the similar mechanisms of m5C and guanosine oxidation, we concluded that 8-oxo-dG could also predict glioma malignancy grade and global DNA demethylation in cancer cells.
Keyphrases
- dna damage
- reactive oxygen species
- circulating tumor
- dna methylation
- cell free
- single molecule
- high grade
- peripheral blood
- oxidative stress
- dna repair
- gene expression
- cell death
- blood pressure
- end stage renal disease
- newly diagnosed
- nucleic acid
- genome wide
- nitric oxide
- ejection fraction
- chronic kidney disease
- multiple sclerosis
- white matter
- brain injury
- prognostic factors
- copy number
- hydrogen peroxide
- young adults
- blood brain barrier
- resting state
- patient reported