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• W3000875478 abstract "ABSTRACT Gliomas are the most common primary brain tumors. High Grade Gliomas have a median survival of 18 months, while Low Grade Gliomas (LGG) have a median survival of ∼7.3 years. Seventy-six percent of patients with LGG express mutated isocitrate dehydrogenase (mIDH1) enzyme (IDH1 R132H ). Survival of these patients ranges from 1-15 years, and tumor mutational burden ranges from 8 to 447 total somatic mutations per tumor. We tested the hypothesis that the tumor mutational burden would predict survival of patients with tumors bearing mIDH1 R132H . We analyzed the effect of tumor mutational burden on patients’ survival using clinical and genomic data of 1199 glioma patients from The Cancer Genome Atlas and validated our results using the Chinese Glioma Genome Atlas. High tumor mutational burden negatively correlates with survival of patients with LGG harboring IDH1 R132H (p<0.0001). This effect was significant for both Oligodendroglioma and Astrocytoma LGG- m IDH1 patients. In the TCGA data, median survival of the high mutational burden group was 76 months, while in the low mutational burden group it was 136 months; p<0.0001. There was no differential representation of frequently mutated genes (e.g., TP53, ATRX, CIC, FUBP ) in either group. Gene set enrichment analysis revealed an enrichment in Gene Ontologies related to Cell cycle, DNA damage response in high vs low tumor mutational burden. Finally, we identified a 19 gene signature that predicts survival for patients from both databases. In summary, we demonstrate that tumor mutational burden is a powerful, robust, and clinically relevant prognostic factor of median survival in mIDH1 patients." @default.
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• W3000875478 date "2020-01-23" @default.
• W3000875478 modified "2023-10-10" @default.
• W3000875478 title "Tumor Mutational Burden Predicts Survival In Patients With Low Grade Gliomas Expressing Mutated IDH1" @default.
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• W3000875478 doi "https://doi.org/10.1101/2020.01.20.20016766" @default.
• W3000875478 hasPublicationYear "2020" @default.
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