机构：[1]Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China四川大学华西医院[2]Department ofPathology, West China Hospital, Sichuan University, Chengdu, 610041, China四川大学华西医院[3]Department of Pathology, TheFirst Hospital of Lanzhou University, Lanzhou, 730000, China[4]Department of Pathology, Peking University ThirdHospital, Beijing, 100191, China[5]Department of Pathology, The First Affiliated Hospital, Zhejiang University,Hangzhou, 310003, China浙江大学医学院附属第一医院[6]Department of Pathology, Xijing Hospital, Air Force Medical University, Xian, 710032,China[7]Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology,Wuhan, 430030, China华中科技大学同济医学院附属同济医院[8]Singlera Genomics Inc., Shanghai, 201318, China
Non-small cell lung cancer (NSCLC) is featured with complex genomic alterations. Molecular profiling of large cohort of NSCLC patients is thus a prerequisite for precision medicine. We first validated the detection performance of a next-generation sequencing (NGS) cancer hotspot panel, OncoAim, on formalin-fixed paraffin-embedded (FFPE) samples. We then utilized OncoAim to delineate the genomic aberrations in Chinese NSCLC patients. Overall detection performance was powerful for mutations with allele frequency (MAF) >= 5% at >500 x coverage depth, with >99% sensitivity, high specificity (positive predictive value > 99%), 94% accuracy and 96% repeatability. Profiling 422 NSCLC FFPE samples revealed that patient characteristics, including gender, age, lymphatic spread, histologic grade and histologic subtype were significantly associated with the mutation incidence of EGFR and TP53. Moreover, RTK signaling pathway activation was enriched in adenocarcinoma, while PI(3)K pathway activation, oxidative stress pathway activation, and TP53 pathway inhibition were more prevalent in squamous cell carcinoma. Additionally, novel co-existence (e.g., variants in BRAF and PTEN) and mutual-exclusiveness (e.g., alterations in EGFR and NFE2L2) were found. Finally, we revealed distinct mutation spectrum in TP53, as well as a previously undervalued PTEN aberration. Our findings could aid in improving diagnosis, prognosis and personalized therapeutic decisions of Chinese NSCLC patients.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81972498, 81601213]; 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZYGD18012]; Key Research and Development Project of Science and Technology Department of Sichuan Province [2017SZ0005]
第一作者机构：[1]Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China[2]Department ofPathology, West China Hospital, Sichuan University, Chengdu, 610041, China[3]Department of Pathology, TheFirst Hospital of Lanzhou University, Lanzhou, 730000, China
通讯作者：
通讯机构：[1]Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China[2]Department ofPathology, West China Hospital, Sichuan University, Chengdu, 610041, China
推荐引用方式(GB/T 7714)：
Jiang Ruirui,Zhang Bo,Teng Xiaodong,et al.Validating a targeted next-generation sequencing assay and profiling somatic variants in Chinese non-small cell lung cancer patients[J].SCIENTIFIC REPORTS.2020,10(1):doi:10.1038/s41598-020-58819-5.
APA：
Jiang, Ruirui,Zhang, Bo,Teng, Xiaodong,Hu, Peizhen,Xu, Sanpeng...&Ye, Feng.(2020).Validating a targeted next-generation sequencing assay and profiling somatic variants in Chinese non-small cell lung cancer patients.SCIENTIFIC REPORTS,10,(1)
MLA：
Jiang, Ruirui,et al."Validating a targeted next-generation sequencing assay and profiling somatic variants in Chinese non-small cell lung cancer patients".SCIENTIFIC REPORTS 10..1(2020)
