TY - JOUR
T1 - Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
AU - Wang, Cheng
AU - Yin, Rong
AU - Dai, Juncheng
AU - Gu, Yayun
AU - Cui, Shaohua
AU - Ma, Hongxia
AU - Zhang, Zhihong
AU - Huang, Jiaqi
AU - Qin, Na
AU - Jiang, Tao
AU - Geng, Liguo
AU - Zhu, Meng
AU - Pu, Zhening
AU - Du, Fangzhi
AU - Wang, Yuzhuo
AU - Yang, Jianshui
AU - Chen, Liang
AU - Wang, Qianghu
AU - Jiang, Yue
AU - Dong, Lili
AU - Yao, Yihong
AU - Jin, Guangfu
AU - Hu, Zhibin
AU - Jiang, Liyan
AU - Xu, Lin
AU - Shen, Hongbing
N1 - Funding Information:
This work was approved by the institutional review board of Nanjing Medical University and all the other participating institutions. This work was supported by the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (81521004), National Key Research and Development Program of China (2017YFC0907905), Science Foundation for Distinguished Young Scholars in Jiangsu (BK20160046), National Natural Science Foundation of China (81573238, 81703295), “333 project” in Jiangsu Province, the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine), and the Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (PPZY2015A067). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
This work was supported by the Science Fund for Creative Research Groups of the National Natural Science Foundation of China (81521004), National Key Research and Development Program of China
Publisher Copyright:
© 2018 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-04492-2
DO - 10.1038/s41467-018-04492-2
M3 - Article
C2 - 29799009
AN - SCOPUS:85047632807
SN - 2041-1723
VL - 9
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2054
ER -