concurrent hypermethylation of dnmt1, mgmt and egfr genes in progression of gliomas并发dnmt1的甲基化,管理和表皮生长因子受体基因在神经胶质瘤的进展.pdfVIP

Gömöri et al. Diagnostic Pathology 2012, 7:8 /content/7/1/8 RESEARCH Open Access Concurrent hypermethylation of DNMT1, MGMT and EGFR genes in progression of gliomas 1* 3 2 2,3 Éva Gömöri , József Pál , Bernadett Kovács and Tamás Dóczi Abstract Background: Gliomas are the most common neoplasm of the brain. High-grade gliomas often resist treatment even with aggressive surgical resection and adjuvant radiation and chemotherapy. Despite the combined treatment, they frequently recur with the same or higher-grade histology. Genetic instability is commonly associated with inactivation of the normal DNA repair function and tumour suppressor genes as well as activation of oncogenes resulting from alterations of promoter hypermethylation, but the molecular mechanisms of the histological and clinical progression of gliomas are still poorly understood. Methods: This study involved longitudinal analysis samples of primary and recurrent gliomas to determine whether the progression of low- and high-grade gliomas is associated with the promoter methylation of the DNMT1, MGMT and EGFR genes by PCR-based restriction enzyme assay. Epigenetic inactivation of these three important glioma-associated genes was analyzed in paired biopsy samples from 18 patients with tumour recurrence. Results: The methylation analysis of the CpG sites in the DNA methyltransferase (DNMT1) promoter revealed a total of 6 hypermethylations (6/18), the methylguanine-DNA methyltransferase (MGMT) promoter revealed a total of 10 hypermethylations (10/18) and the epithelial grow factor receptor (EGFR) promoter revealed a total of 12 (12/ 18) hypermethylations respectively in recurrent gliomas. The results demonstrated that DNMT1 promoter hypermethylation does not occur