Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients.
Cheng WangRong YinJuncheng DaiYayun GuShaohua CuiHongxia MaZhihong ZhangJiaqi HuangNa QinTao JiangLiguo GengMeng ZhuZhening PuFangzhi DuYuzhuo WangJianshui YangLiang ChenQianghu WangYue JiangLili DongYihong YaoGuangfu JinZhibin HuLiyan JiangLin XuHongbing ShenPublished in: Nature communications (2018)
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.
Keyphrases
- small cell lung cancer
- end stage renal disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- epidermal growth factor receptor
- mass spectrometry
- tyrosine kinase
- multiple sclerosis
- genome wide
- ms ms
- peritoneal dialysis
- risk assessment
- dna methylation
- advanced non small cell lung cancer
- patient reported outcomes
- single cell
- deep learning
- genome wide identification