P12.07.b Rare Germline Variants Contribute to Glioma Predisposition

BACKGROUND Gliomas are the most common malignant primary brain tumors in adults and are associated with high mortality, particularly at higher grades. While familial syndromes and common genetic risk factors are relevant in glioma susceptibility, the role of rare germline variants in individuals without a known family history remains poorly defined. Identifying such variants could enhance our understanding of glioma predisposition MATERIAL AND METHODS We conducted whole-genome sequencing (WGS) on a cohort of 113 glioma patients from a biobank in Northern Sweden. Rare variants were evaluated within a predefined gene set relevant to cancer and glioma biology. To contextualize our findings, we compared variant frequencies with multiple independent control datasets, including local population controls and publicly available genomic resources. External validation was performed using several independent glioma datasets. RESULTS A notable proportion of glioma patients carried rare germline variants classified as pathogenic or likely pathogenic. Burden analyses indicated a significant enrichment of rare variants in genes not previously implicated in glioma predisposition. These findings suggest the presence of underlying genetic susceptibility factors beyond known familial syndromes, potentially affecting a subset of glioma patients with sporadic disease presentation. CONCLUSION Our findings support the contribution of rare germline variants to glioma risk in a non-familial context. While specific gene associations still need evaluation, the results underscore the potential for integrating germline genomic profiling in future glioma risk assessment.