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- W4214817744 abstract "Abstract Background: Current variability in methods for tumor mutational burden (TMB) estimation and reporting urges the need for a homogeneous TMB assessment. Here we compared the TMB distributions in different cancer types using two customized targeted panels commonly used in clinical practice. Methods: TMB spectrum of the 295- and 1021-Gene panels in multiple cancer types were compared using targeted next-generation sequencing (NGS). Then the TMB distributions across a diverse cohort of 2,332 cancer cases were investigated for their associations to clinical features. Treatment response data was collected for 222 patients who received immune-checkpoint inhibitors (ICIs) and their homologous recombination DNA damage repair (HR-DDR) and PD-L1 expression were additionally assessed, and compared with TMB and response rate. Results: The median TMB between the gene panels were similar despite wide range in TMB values. Highest TMB was 8 and 10 in patients with squamous cell carcinoma and esophageal carcinoma according to the classification of histopathology and cancer types, respectively. Patients with high TMB and HR-DDR positive status could benefit from ICIs therapies (23 patients versus 7 patients with treatment response, P = 0.004). Additionally, PD-L1 expression was not associated with TMB and treatment response among patients receiving ICIs. Conclusions: Targeted NGS assays demonstrated advantageous ability to evaluate TMB in pan-cancer samples as a tool to predict response to ICIs. Also, TMB integrated with HR-DDR positive status could be a significant biomarker for predicting ICIs response in patients." @default.
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- W4214817744 date "2020-08-03" @default.
- W4214817744 modified "2023-09-26" @default.
- W4214817744 title "Pan-cancer analysis of tumor mutational burden and homologous recombination DNA damage repair by targeted next-generation sequencing" @default.
- W4214817744 doi "https://doi.org/10.21203/rs.3.rs-49293/v1" @default.
- W4214817744 hasPublicationYear "2020" @default.
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