The analysis of deregulated expression and methylation of the PER2 genes in gliomas.

CONTEXT: Growing evidence shows that disruption of circadian rhythm may be a risk factor in the development of glioma. However, the molecular mechanisms of genes controlling circadian rhythm in glioma cells have not been explored and differential expression of the circadian clock genes in glioma and non-tumor cells may provide a molecular basis for manifesting this mechanism. AIMS: The aim of the following study is to analyze the PER2 expression involved in the pathogenesis of glioma. MATERIALS AND METHODS: Using immunohistochemical staining, methylation specific polymerase chain reaction techniques, we examined the expression of the most important clock genes, PER2, in 92 gliomas. STATISTICAL ANALYSIS USED: The association between tumor grade (high-grade/low-grade gliomas) and expression of the investigated proteins (negative/positive) was assessed using the Spearman, Chi-square test and two-sample t-test, included in the Statistical Package for the Social Science, version 13.0. Using Spearman Correlation to analyse correlation between the expression of PER 2 and PER2 promoter methylation. RESULTS: Our results reveal disturbances in the expression of the period 2 (PER2) genes in most (52.17%) of the glimoa cells in comparison with the nearby non-cancerous cells and the PER2 gene deregulation is most probably by methylation of the PER2 promoter. CONCLUSIONS: Since, the circadian clock controls expression of cell-cycle related genes, we suggest that disturbances in PER2 gene expression may result in disruption of the control of the normal circadian clock, thus benefiting the survival of cancer cells and promoting carcinogenesis. Differential expression of circadian genes in non-cancerous and cancerous cells may provide a molecular basis for chronotherapy of glioma.

Deregulated expression of cry1 and cry2 in human gliomas.

Growing evidence shows that deregulation of the circadian clock plays an important role in the development of malignant tumors, including gliomas. However, the molecular mechanisms of gene chnages controlling circadian rhythm in glioma cells have not been explored. Using real time polymerase chain reaction and immunohistochemistry techniques, we examined the expression of two important clock genes, cry1 and cry2, in 69 gliomas. In this study, out of 69 gliomas, 38 were cry1-positive, and 51 were cry2-positive. The expression levels of cry1 and cry2 in glioma cells were significantly different from the surrounding non-glioma cells (P<0.01). The difference in the expression rate of cry1 and cry 2 in high-grade (grade III and IV) and low-grade (grade 1 and II) gliomas was non-significant (P>0.05) but there was a difference in the intensity of immunoactivity for cry 2 between high-grade gliomas and low-grade gliomas (r=-0.384, P=0.021). In this study, we found that the expression of cry1 and cry2 in glioma cells was much lower than in the surrounding non-glioma cells. Therefore, we suggest that disturbances in cry1 and cry2 expression may result in the disruption of the control of normal circadian rhythm, thus benefiting the survival of glioma cells. Differential expression of circadian clock genes in glioma and non-glioma cells may provide a molecular basis for the chemotherapy of gliomas.