MT1 gene cluster methylation analysis in astrocytic gliomas

Abstract

Background and aim: Astrocytic gliomas are the most common brain tumors characterized by high molecular heterogeneity, resistance to therapy and rapid progression. Despite advance in therapy, the most malignant form of astrocytic glioma, glioblastoma still determine poor survival rate, approximately 3-9 months. Thus, molecular markers for diagnosis and prognosis are urgently required. Metallothioneins (MTs) are group of cysteine-rich, metal-binding proteins encoded by aset of genes located on chromosome 16q12.2-q13. It was shown that in cancerous cells DNA methylation can span in long stretches or gene clusters of the genome, contributing to gene expression. MT1 gene cluster is known for DNA methylation in several cancers which could serve as patient outcome biomarker. There is no data for MT1 cluster methylation level in astrocytic gliomas and its contribution to patient outcome. Materials and methods: Methylation of 10 CpG islands (CGIs) at MT1 cluster in 68 post-operative tissues of patients with different grade astrocytic gliomas was determined by MS-PCR. Methylation levels were estimated and associations with patient clinical characteristics were analyzed. CGI methylation score was calculated for survival prognosis using Kaplan-Meier method. Significance level chosen for analysis was p<0.05. [...].