Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients
| Autor: | Juncheng Dai, Jianshui Yang, Na Qin, Lin Xu, Liyan Jiang, Yuzhuo Wang, Yayun Gu, Fangzhi Du, Tao Jiang, Hongbing Shen, Shaohua Cui, Zhibin Hu, Cheng Wang, Zhihong Zhang, Zhening Pu, Rong Yin, Yihong Yao, Meng Zhu, Jiaqi Huang, Yue Jiang, Lili Dong, Qianghu Wang, Liguo Geng, Hongxia Ma, Liang Chen, Guangfu Jin |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male China Lung Neoplasms Lymphocyte Science General Physics and Astronomy Genomics Biology medicine.disease_cause General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Asian People Carcinoma Non-Small-Cell Lung medicine Carcinoma Tumor Microenvironment Humans lcsh:Science Lung cancer Gene Aged Whole genome sequencing Aged 80 and over Tumor microenvironment Mutation Multidisciplinary Whole Genome Sequencing General Chemistry Middle Aged medicine.disease respiratory tract diseases ErbB Receptors 030104 developmental biology medicine.anatomical_structure Cancer research lcsh:Q Female |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-10 (2018) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The distinct genomic and epidemiological features of Chinese lung cancer patients suggest the presence of alternative causal mechanisms. Here, the authors present the genomic landscape of 149 Chinese NSCLC patients and reveal distinct mutational signatures associated with inflammatory microenvironments. |
| Databáze: | OpenAIRE |
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