Tumor Mutation Burden Derived From Large Ngs Panel As Biomarker For Immunotherapy Response

JOURNAL OF CLINICAL ONCOLOGY(2017)

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摘要
e23077Background: Tumor mutation burden (TMB) is an informative biomarker for predicting response to immunotherapy in a growing number of malignancies. The TMB clinical applicability is limited due to cost and bioinformatics requirements of sequencing and analyis of whole exome/gemone. Here, we demonstrate that a large next generation sequencing (NGS) panel can accurately identify hypermutation status. Methods: A novel algorithmic approach to derive the predicted total mutation load (PTML) described in J Roszik et al, BMC Med, 2016, was applied to our large NGS panel, CANCERPLEX. Statistical weights were calculated for each of the genes using publically available TCGA database. The algorithm was tested using CANCERPLEX data of stomach adenocarcinoma (199), colorectal cancer (59), and lung cancer (60) cohorts (n = 318). The correlation of PTML status with mismatch repair (MMR) status (n = 11) was also tested. The correlation of PTML status with clinical outcome was assessed using WES data following distinc...
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