PATH-37. PROGNOSTIC IMPACT OF TUMOR MUTATIONAL BURDEN AT BASELINE IN IDH-WILDTYPE GLIOBLASTOMA

Abstract

Abstract Tumor mutational burden (TMB) has emerged as a potential biomarker for survival and response to immune checkpoint therapy. However, limited data are available regarding the prognostic impact of TMB at baseline in glioblastoma (GBM). This study aimed to evaluate the somatic mutation status and survival outcomes of isocitrate dehydrogenase (IDH) wildtype GBM using a dataset of GBM samples from cBioPortal and single tertiary hospital. A total of 840 samples were extracted from cBioPortal, including 410 samples from Memorial Sloan Kettering Cancer Center (MSKCC), 234 samples from The Cancer Genome Atlas (TCGA), 106 samples from Glioma Longitudinal Analysis Consortium (GLASS), and 90 samples from Clinical Proteomic Tumor Analysis Consortium (CPTAC). Additionally, we enrolled 341 GBM patients with targeted sequencing data (OncoPanel AMC) from Asan Medical Center. The TMBHigh group was defined as the top 10% value of TMB within each cohort. Among the total of 1,081 IDH-wt GBM samples, 104 samples were classified as TMBHigh. No significance difference in overall survival (OS) was observed between the TMBHigh group and the non-TMBHigh group across the 5 cohorts. The mutations of DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and POLE) was significantly higher in the TMBHigh group compared with the non-TMBHigh group in 3 of 5 cohorts (pASAN=1.02x10-4, pMSKCC=1.5x10-2, and pCPTAC=1.26x10-2). However, when we calculated the indel to total mutation ratio (I-index) to dedect microsatellite Instability, only the MSKCC cohort showed a higher I-index in the TMBHigh group compared to the non-TMBHigh group (16.7% vs 13.7%, p=2.67x10-3). In summary, there is no significant association between TMB at baseline and poor survival outcomes in IDH-wildtype GBM. Further research is needed to explore the potential implications of TMB as a prognostic marker and its relevance for personalized treatment strategies in GBM patients.