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Evaluation of 30 DNA damage response and 6 mismatch repair gene mutations as biomarkers for immunotherapy outcomes across multiple solid tumor types

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Cancer Biology & Medicine 2021年第4期18卷 1080-1091页

作者： Zhe Gong Yue Yang Jieyun Zhang Weijian Guo Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China

Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)***,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI ***:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published *** Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from ***:Six MMR and 30 DDR genes were included in this *** MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the *** MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer ***:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.

关键词： Immune checkpoint inhibitor therapy prediction of efficacy tumor mutation burden mismatch repair deficiency DNA damage response genes

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