Cbio-12. GTP Metabolic Switch Leads to Nucleolar Transformation and Malignant Growth of Glioblastoma

Abstract

NEURO-ONCOLOGY • NOVEMBER 2017and post-treatment glioblastoma tumours were subjected to gene expression profiling (Fluidigm, TaqMan assays), MGMT promoter methylation analysis (pyrosequencing) and protein expression analysis of the DNA repair pathways, known to be involved in treatment resistance (immunohistochemistry). Gene expression profiling used to molecularly subtype tumours revealed that 26% of recurrent post-treatment specimens did not match their primary diagnostic specimen. Post-treatment specimens had molecular changes which correlated with known resistance mechanisms including increased expression of APEX1 (p<0.05) and altered MGMT methylation status. Increased expression of GPNMB, CCL5 and KLRC1 (associated with immune suppression, invasion and aggression) and polarisation towards an M2 phenotype (anti-inflammatory and immune suppressive) in post-treatment tumours demonstrated an overall change in the tumour microenvironment favouring aggressive tumour growth and disease progression. These findings highlight the ability of glioblastomas to evade not only the toxic onslaught of therapy but also to evade the immune system suggesting that immune-altering therapies may be of value in treating this terrible disease. CBIO-11.