Driver gene alterations profiling of Chinese non‐small cell lung cancer and the effects of co‐occurring alterations on immunotherapy

作者：Shengjie Sun, Wenjuan Du, Qiong Sun, Xiao Zhao, Boyu Qin, Duozhi Shi, Chong Wan, Zhi‐Yong Wu · 发表于：Cancer Medicine · 年份：2021 · DOI：10.1002/cam4.4178 · 被引用次数：13 · 研究领域：Lung Cancer Treatments and Mutations、Cancer Immunotherapy and Biomarkers、Cancer Genomics and Diagnostics

BACKGROUND: Molecular testing for alterations in oncogenic driver genes and targeted therapies have become standard procedures for non-small cell lung cancer (NSCLC) patients. However, little evidence has shed light on the pattern of co-existence of driver genes in NSCLC, and whether they may have different tumor features affecting immunotherapy is still unclarified. METHODS: Genomic alterations in 14 lung cancer-related genes were conducted in 3440 Chinese NSCLC patients using next-generation sequencing. Meanwhile, tumor mutational burden and immunotherapy dataset from the Memorial sloan kettering cancer center (MSKCC) and lung adenocarcinoma dataset from The Cancer Genome Atlas (TCGA) were utilized for analyzing the impact of the co-occurring alterations on patients' survival following immunotherapy. RESULTS: In this cohort, 90.17% of patients had at least one somatic alteration in the 14 genes, including 51% of co-occurring alterations. TP53 and epidermal growth factor receptor (EGFR) were the most prevalent genes (54.74% and 53.55%, respectively), followed by KRAS, ERBB2, ALK, PIK3CA, ROS1, RET, MET, BRAF, KIT, FGFR1, PDGFRA, and NRAS. The prevalence of TP53, EGFR, and ERBB2 in our cohort were significantly higher than that from the TCGA database, whereas KRAS, BRAF, and PDGFRA were significantly lower than the latter. Furthermore, the patients who harbored multiple alterations (8.86%, 31/350) in eight driver genes survived longer and have a higher tumor mutation burden c...