Exome And Transcriptome Profiling Of Lung Adenocarcinoma In Female Never-Smokers

Background: Lung cancer is the leading cause of cancer-related mortality in the world. TCGA projects for lung adenocarcinoma and squamous cell carcinoma are the largest datasets publicly available so far. They include diverse subtypes and population groups and thus small population groups such as female never-smokers in Asian are under-represented. Female never-smokers are an important population cohort where mutations due to genetic factors are enriched rather than environmental factors such as smoking. We applied the high throughput deep sequencing strategy to catalog somatic mutations and to profile gene expression levels for Korean patients. Results: Deep sequencing data of exome and transcriptome were generated for tumor and matched normal tissues from 100 non-small-cell lung cancer (NSCLC) patients in female never-smokers. The mutational catalogue includes numerous somatic mutations, indels, and gene-fusion events. Comparison with TCGA lung cancer data shows that our patients harbor much less and homogeneous somatic mutations as expected. Mutational frequency and driver gene analyses identified many novel candidates of causal genetic variations. For example, our mutation spectrum reveals 5 key modules of enriched somatic mutations such as EGFR, p53, Wnt signaling pathways, ECM organization, and cell cycle checkpoints. Furthermore, network analysis of integrating mutation and expression data illustrates the detailed mechanism of dysregulation in tumorigenesis of lung adenocarcinoma. Conclusion: Our study elucidates clinically important mutations and regulatory elements in NSCLC. It is expected that our dataset would serve as an important resource for lung cancer research especially in Asian populations. Citation Format: Sanghyuk Lee, Pora Kim, Yukyung Jun, Charny Park, Suyeon Kim, Hee-Young Lee, Juhee Keum, Yeonhwa Jung, Yeonjoo Jung, Chaehwa Seo, Kyoohyoung Rho, Jong-Eun Lee, Wankyu Kim, Jaesang Kim, Jhingook Kim. Exome and transcriptome profiling of lung adenocarcinoma in female never-smokers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1532. doi:10.1158/1538-7445.AM2014-1532