GENE-46. COMPARISON OF MATCHED GLIOBLASTOMA TUMOR AND MARGIN SAMPLES USING SINGLE BASE RESOLUTION MAPS REVEALS ACQUIRED, EARLY EPIGENETIC CHANGES THAT PREDISPOSE TO MUTATIONS DURING TUMOURIGENESIS

METHODSWe performed whole genome sequencing (100x coverage) and total RNA sequencing of blood, tumor and margin samples from a patient with de-novo glioblastoma (GB). Oxidative bisulfite sequencing and bisulfite sequencing were employed on PCR-free DNA libraries to generate high-depth (80x) coverage and build single base resolution maps that distinguished 5mC and 5hmC modifications.RESULTSEnhanced (hydroxyl)-methylome sequencing reveals global hypermethylation in the tumor with average levels of 60% 5mC and drastic loss of 5hmC to 1.6%. In the margin we found levels of 50% 5mC and 20% for 5hmC integrated over all CpGs in the genome. CpGs with high levels of 5hmC in the margin had correspondingly higher levels of 5mC in the tumor. We analysed the mutational landscape by identifying single nucleotide variants (SNVs) in the tumor and margin using the blood sample as a …