Tumour Mutational Burden is Associated with Poor Outcomes that Cannot Be Predicted by Pan-cancer Targeted Sequencing in Diffused Glioma

Aims Tumor mutational burden (TMB) is a biomarker for immune checkpoint therapy. The impact of TMB on clinical outcomes and the correlation coefficient between exome sequencing and targeted sequencing in glioma have not yet been explored. Methods Somatic mutations in the coding regions of 897 primary gliomas, clinical and RNA-seq information for 654 patients In TCGA dataset were analyzed. Descriptive and correlational analyses were conducted with TMB. Enrichment Map and GSEA was also performed. Results TMB was higher for the group of mutant genes that are frequently mutated in glioblastomas (GBMs) and lower for the group of mutant genes that are frequently mutated in lower-grade gliomas (LGGs). Patients with a higher TMB exhibited shorter overall survival. TMB was associated with grade, age, subtype and mutations affecting genomic structure. The signaling pathways of the cell cycle and immune effector processes were enriched in the TMBHigh group. TMB was higher in the mismatch repair (MMR) gene mutant group compared to the wildtype group, but the MMR pathway was enriched in the TMBHigh group of gliomas without mutations in classical MMR genes. The correlation between TMBs calculated through exome sequencing and targeted sequencing was moderate. Conclusions TMB is associated with poor outcomes in diffuse glioma. High proliferative activity in the TMBHigh group could account for the shorter survival of these patients. This association was not reflected by a pan-cancer targeted sequencing panel.