Abstract 5375: Whole-genome sequencing reveals genomic signatures associated with the immunologic microenvironments in Chinese NSCLC patients

Abstract

Abstract Over the past decades, next-generation sequencing has accelerated the systematic characterization of genomic events, including single base substitutions and small insertions/deletions (indels), and has yielded substantial insights into the unique and shared genomic features of the two NSCLC subtypes. Genomic studies of lung cancer have mainly been conducted in patients from Western countries; however, Chinese lung cancer patients have distinct epidemiologic and genomic features, highlighting the presence of specific etiologic mechanisms in addition to smoking. To reveal the underlying mechanisms, we presented a comprehensive genomic landscape of 149 Non-Small Cell Lung Cancer (NSCLC) cases. We identified 15 potential driver genes and three mutational signatures, two of which have been connected with APOBEC enzymes and smoking. In addition, we revealed that Chinese patients are specially characterized by not only highly clustered and functional EGFR mutations but also a mutational signature, that is associated with inflammatory tumor-infiltrating lymphocytes (P = 0.001). The EGFR mutation rate is significantly increased with the proportion of the MS3 signature (P<0.001). As a classic tumor-enabling hallmark, inflammatory infiltration may contribute to the accumulation of EGFR mutations, especially in never-smokers. Additionally, patients with a higher proportion of the MS3 signature carried a higher contribution of characterized chromosomal rearrangements (P<0.001). The results revealed specific genomic features in the inflammatory microenvironments in Chinese patients with potential implications for understanding the etiology, prevention and therapy of NSCLC. Citation Format: Cheng Wang, Juncheng Dai, Yayun Gu, Zhibin Hu, Hongbing Shen. Whole-genome sequencing reveals genomic signatures associated with the immunologic microenvironments in Chinese NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5375.