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

• DOI: 10.1038/s41467-018-04492-2
• Publication Date: 2018-05-20T19:49:54Z
• Authors: 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; Hongbing Shen
• Keywords: Adult; Aged, 80 and over; Male; China; 0303 health sciences; Lung Neoplasms; Whole Genome Sequencing; Science; Q; Genomics; Middle Aged; Article; 3. Good health; ErbB Receptors; 03 medical and health sciences; Asian People; Carcinoma, Non-Small-Cell Lung; Mutation; Tumor Microenvironment; Humans; Female; Aged

AbstractChinese 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.