Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients

Cheng Wang, Rong Yin, Juncheng Dai, Yayun Gu, Shaohua Cui, Hongxia Ma, Zhihong Zhang, Jiaqi Huang, Na Qin, Tao Jiang, Liguo Geng, Meng Zhu, Zhening Pu, Fangzhi Du, Yuzhuo Wang, Jianshui Yang, Liang Chen, Qianghu Wang, Yue Jiang, Lili Dong, Yihong Yao, Guangfu Jin, Zhibin Hu, Liyan Jiang (), Lin Xu () and Hongbing Shen ()
Additional contact information
Cheng Wang: School of Public Health, Nanjing Medical University
Rong Yin: Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research
Juncheng Dai: School of Public Health, Nanjing Medical University
Yayun Gu: School of Public Health, Nanjing Medical University
Shaohua Cui: Shanghai Chest Hospital, Shanghai Jiao Tong University
Hongxia Ma: School of Public Health, Nanjing Medical University
Zhihong Zhang: First Affiliated Hospital, Nanjing Medical University
Jiaqi Huang: Cellular Biomedicine Group, Inc.
Na Qin: School of Public Health, Nanjing Medical University
Tao Jiang: School of Public Health, Nanjing Medical University
Liguo Geng: School of Public Health, Nanjing Medical University
Meng Zhu: School of Public Health, Nanjing Medical University
Zhening Pu: School of Public Health, Nanjing Medical University
Fangzhi Du: School of Public Health, Nanjing Medical University
Yuzhuo Wang: School of Public Health, Nanjing Medical University
Jianshui Yang: School of Public Health, Nanjing Medical University
Liang Chen: Nanjing Medical University
Qianghu Wang: School of Biomedical Engineering and Informatics, Nanjing Medical University
Yue Jiang: School of Public Health, Nanjing Medical University
Lili Dong: Shanghai Chest Hospital, Shanghai Jiao Tong University
Yihong Yao: Cellular Biomedicine Group, Inc.
Guangfu Jin: School of Public Health, Nanjing Medical University
Zhibin Hu: School of Public Health, Nanjing Medical University
Liyan Jiang: Shanghai Chest Hospital, Shanghai Jiao Tong University
Lin Xu: Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research
Hongbing Shen: School of Public Health, Nanjing Medical University

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. Here, we present a comprehensive genomic landscape of 149 non-small cell lung cancer (NSCLC) cases and identify 15 potential driver genes. We reveal that Chinese patients are specially characterized by not only highly clustered EGFR mutations but a mutational signature (MS3, 33.7%), that is associated with inflammatory tumor-infiltrating B lymphocytes (P = 0.001). The EGFR mutation rate is significantly increased with the proportion of the MS3 signature (P = 9.37 × 10−5). TCGA data confirm that the infiltrating B lymphocyte abundance is significantly higher in the EGFR-mutated patients (P = 0.007). Additionally, MS3-high patients carry a higher contribution of distant chromosomal rearrangements >1 Mb (P = 1.35 × 10−7), some of which result in fusions involving genes with important functions (i.e., ALK and RET). Thus, inflammatory infiltration may contribute to the accumulation of EGFR mutations, especially in never-smokers.

Date: 2018
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DOI: 10.1038/s41467-018-04492-2

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