Chromatin accessibility and DNA methylation changes associated with high and low Glioma-CpG island methylator phenotype (G-CIMP)

Abstract

Malignant gliomas are quite heterogeneous brain tumors characterized by progression and recurrence with highly variable patterns and intervals. The World Health Organization established both histological and molecular features to classify gliomas in 2016, being IDH mutation the most predictive biomarker. So far, this alteration was associated with favorable clinical outcome and increased DNA methylation levels at CpG islands (G-CIMP). However, a recent study showed a subclassification for G-CIMP tumors: G-CIMP-low, with a lower DNA methylation profile associated with significantly worse survival and abnormalities in cell cycle pathway genes, and G-CIMP-high, with higher global levels of DNA methylation and better clinical outcome. Moreover, there are evidences showing a potential progression from G-CIMP-high to G-CIMP-low. The aim of this project is to study the progression mechanism through G-CIMP samples using Whole Genome Bisulfite Sequencing (WGBS) to assess changes in DNA methylation that may lead to alterations in chromatin accessibility, therefore, causing deregulation of coding genes. This effort will require generation of new data and integration with publicly available data in order to achieve better understanding of the epigenetic landscape from G-CIMP-low and G-CIMP-high samples. (AU)