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

被引：79

作者：

Wang, Cheng ^{[1
,2
,3
]}

Yin, Rong ^{[4
]}

Dai, Juncheng ^{[1
,2
]}

Gu, Yayun ^{[1
,2
]}

Cui, Shaohua ^{[5
]}

Ma, Hongxia ^{[1
,2
]}

Zhang, Zhihong ^{[6
]}

Huang, Jiaqi ^{[7
]}

Qin, Na ^{[1
,2
]}

Jiang, Tao ^{[1
,2
]}

Geng, Liguo ^{[1
,2
]}

Zhu, Meng ^{[1
,2
]}

Pu, Zhening ^{[1
,2
]}

Du, Fangzhi ^{[1
,2
]}

Wang, Yuzhuo ^{[1
,2
]}

Yang, Jianshui ^{[1
,2
]}

Chen, Liang ^{[8
]}

Wang, Qianghu ^{[3
]}

Jiang, Yue ^{[1
,2
]}

Dong, Lili ^{[5
]}

Yao, Yihong ^{[7
]}

Jin, Guangfu ^{[1
,2
]}

Hu, Zhibin ^{[1
,2
]}

Jiang, Liyan ^{[5
]}

Xu, Lin ^{[4
]}

Shen, Hongbing ^{[1
,2
]}

机构：

[1] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing 211116, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing 211116, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Sch Biomed Engn & Informat, Dept Bioinformat, Nanjing 211116, Jiangsu, Peoples R China

[4] Nanjing Med Univ, Dept Thorac Surg, Jiangsu Canc Hosp, Jiangsu Inst Canc Res,Affiliated Canc Hosp,Jiangs, Nanjing 210029, Jiangsu, Peoples R China

[5] Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Resp Med, Shanghai 200030, Peoples R China

[6] Nanjing Med Univ, Affiliated Hosp 1, Dept Pathol, Nanjing 210029, Jiangsu, Peoples R China

[7] Cellular Biomed Grp Inc, Shanghai 200233, Peoples R China

[8] Nanjing Med Univ, Affiliated Hosp 1, Dept Thorac Surg, Nanjing 210029, Jiangsu, Peoples R China

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

中国国家自然科学基金;

关键词：

MUTATIONAL PROCESSES; SOMATIC MUTATIONS; LUNG-CANCER; LANDSCAPE; IMMUNE; ADENOCARCINOMA; ALIGNMENT; ULTRAFAST; PACKAGE; GENES;

D O I：

10.1038/s41467-018-04492-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 x 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 x 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.

引用

页数：10

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