Abstract
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.
Highlights
Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking
According to a specific mutational signatures (MSs), our results revealed that Chinese non-small cell lung cancer (NSCLC) patients were enriched with inflammatory tumorinfiltrating lymphocytes (TILs) (B and CD4+ T lymphocytes)[28]
The results indicated that the immunologic microenvironments occurred in the initial stage of lung cancer and emphasized their essential role in the development of lung cancer
Summary
Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms other than smoking. We present a comprehensive genomic landscape of 149 non-small cell lung cancer (NSCLC) cases and identify 15 potential driver genes. Genomic studies of lung cancer have mainly been conducted in patients from Western countries[2,3,4]; Chinese patients have unique epidemiological features, especially women. The lung cancer rates are higher in Chinese women than among women in some European countries despite an extremely low prevalence of smoking[1], indicating the presence of other carcinogens and carcinogenic mechanisms. The inverse mutation rates of EGFR and KRAS in Chinese NSCLC patients[6] have provided some clues for the etiologic mechanisms, but the full picture remains unclear
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