Low-grade Gliomas In The IDH1 Gene Mutation Hif-1α Gene Expression Relations

Mutations of isocitrate dehydrogenases1(IDH1) are frequently occurred in WHO Ⅱ and Ⅲ Astrocytoma and Oligodendroglioma as well as secondary Glioblastoma. Over90%of these mutations specifically affect the codon132of IDH1gene, and approximately90%mutations resulted in the replacement of the arginine residue by histidine(R132H). According to plenty of clinical researches, patients with IDH1gene mutations represented a better prognosis compared with those harboring wildtype IDH1gene, and meanwhile, patients with IDH1mutations showed enhanced sensitivity to radiation therapy.According to some researches, the2-hydroxyglutarate (2-HG), specially produced by the mutant IDH1, could inhibit the activities of proline hydroxylase-2(PHD2) and hence inhibit the downgraduation of the hypoxia-inducible factor1alpha (Hif-1α) in glioma cells by which resulted in the upregulation the Hif-1α protein level; The evidence from other work supported the idea that mutant IDH1promoted the activity of EGLN prolyl hydroxylases and consequently led to the degradation of Hif-1α. However, other two independent researches did not find any significant relation between mutant IDH1and the Hif-1α level in glioma samples. So far, there is no published work demonstrating the relationship between IDH1mutations and Hif-1α mRNA expression level in clinical glioma samples.Based on the current researches, we explored the accurate relationship between the IDH1mutations and Hif-1α gene as well as its target gene, GAPDH, on the mRNA level. By analyzing43WHO Ⅱ and Ⅲ glioma samples, we found no significant association between IDH1mutations and the Hif-la mRNA expression level. But the mRNA expression of GAPDH were significantly downgraduated in those glioma samples with IDH1mutation. As a conclusion, the IDH1gene mutation dose not regulate the Hif-la expression on the transcriptional level but does influent the Hif-la mediated signaling pathway through enhancing the downgraduation of Hif-1α.