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- W4281782912 abstract "2631 Background: Tumor mutation burden (TMB) has been validated as a biomarker to predict the response of immune checkpoint inhibitors (ICIs) treatment in various cancers. However, the effects of different sequencing platforms, cancer types and calculation methods on TMB as well as its cut-off value for predicting immunotherapy efficacy are still need to be further investigated. Methods: 4140 tumor samples were performed with targeted panel sequencing or whole exome sequencing (WES) in different platforms such as illumina and MGI. Public sequencing data from 3680 samples which contained targeted panel sequencing, WES and whole genome sequencing were obtained. The impact of different sequencing platforms, sequencing methods and calculation methods on the calculation of TMB were assessed. Further, targeted panel sequencing data from 71 sample of lung cancer patients treated with ICIs were used to determine the best cut-off value of TMB for predicting immunotherapy response. Results: TMB values calculated by different platforms and different sequencing methods were similar and there was no significant difference. The distribution of TMB at different sequencing depths and tumor purity were analyzed. We found that there was no significant difference in the distribution of TMB when the sequencing depth was greater than 500´, the HE purity was greater than 0.1 or NGS purity was greater than 0.3. In addition, the correlation of TMB calculated from single-sample and paired-sample is 0.95. Further, the optimal cut-off value of TMB in lung cancer treated with ICIs was determined to be 8 through ROC curve analysis, and patients with TMB ≥ 8 had better outcomes than patients with TMB < 8. Conclusions: This study systematically analyzed the factors which influenced the TMB calculation, and verifies the feasibility of TMB calculation from single-sample. More importantly, the cut-off value of TMB for predicting immunotherapy efficacy in lung cancer was defined as 8 in East Asian populations, which can help in clinical decision-making." @default.
- W4281782912 created "2022-06-13" @default.
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- W4281782912 date "2022-06-01" @default.
- W4281782912 modified "2023-10-07" @default.
- W4281782912 title "Systematic assessment of tumor mutational burden calculation across different sequencing platforms and cancer types and its implication in clinical decision-making." @default.
- W4281782912 doi "https://doi.org/10.1200/jco.2022.40.16_suppl.2631" @default.
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