EPID-30. Abundance of Transposable Elements is Associated with inferior Survival in IDH-wildtype Glioblastoma: A TCGA analysis

Abstract INTRODUCTION IDH-wildtype glioblastoma (GBM) is an aggressive brain tumor with limited therapeutic options and poor prognosis. Growing evidence suggests that transposable elements (TEs) may play critical roles in cancer by promoting genomic instability, altering gene expression through insertional mutagenesis, and modulating immune responses via the expression of TE-derived neoantigens, but their specific impact on IDH-wildtype GBM remains unclear. We investigated the association of TE abundance with survival and oncogenic pathways in GBM. METHODS We analyzed RNA-sequencing data from 151 IDH-wildtype GBM tumors, classified per WHO 2021 guidelines. TE abundance was quantified in tumor samples across genomic regions (whole genomic, exonic, intronic, intergenic) using REdiscoverTE. Associations with overall survival were evaluated using Cox proportional hazards models. Pathway enrichment analyses were performed for genes correlated with survival-associated TEs. RESULTS Increased abundance of several TEs was significantly associated with reduced survival. Notably, whole-genome BC200 abundance was linked to poorer survival (HR1.75, 95% CI:1.28-2.22, p= 0.0042), with high expressors having a median survival of 9.81 vs 14.7 months. Similarly, LTR7Y (HR=2.24, 95%CI: 1.55-3.25, p=0.011), MER61D (HR=1.48, 95%CI: 1.20-1.82, p=0.055), and exonic L1ME3B (HR=2.27, 95% CI: 1.5-3.44, p=0.022) were significantly associated with inferior survival. These survival associations were independent of MGMT promoter methylation and CDKN2A deletion status. Gene expression correlated with TE abundance revealed enrichment in pathways related to RNA processing (BC200) L1mE3B), cellular motility and axon guidance (LTR7Y, MER61D), and immune regulation (LTR16A), suggesting potential multifaceted roles in GBM progression. CONCLUSION Our findings demonstrate that specific TEs are significantly associated with inferior survival in IDH-wildtype GBM, highlighting their potential as prognostic markers alongside known somatic mutations. Their association with key tumorigenic processes such as immune evasion and genomic instability further suggests a contributory role in tumor progression and identifies them as potential therapeutic targets. Future studies should investigate the mechanistic functions, regulatory dynamics, and tissue specificity of TEs using longitudinal datasets to better elucidate their role in GBM biology.