Journal Article

Genomic landscape of lung adenocarcinoma in East Asians

Teo, Audrey Su Min, Nahar, Rahul, Chua, Khi Pin, Lim, Jia Qi, Phua, Cheryl Zi Jin, Aung, Zaw Win, Takano, Angela, Lee, Yi Fei, Choi, Poh Sum, Alvarez, Jacob Josiah Santiago, Ong, Boon-Hean, Sherbaf, Faranak Ghazi, Zhai, Weiwei, Lee, Yin Yeng, Tam, Wai Leong, Hsu, Anne Ann Ling, Creasy, Caretha L., Lu, Bingxin, Hillmer, Axel M., Tan, Daniel Shao Weng, Koh, Tina Puay Theng, Too, Chow Wei, Liu, Jin, Suteja, Lisda, Ma, Siming, Lim, Wan-Teck, Lim, Bing, Tan, Chu Quan, Chen, Pauline Jieqi, Anantham, Devanand, Toh, Chee Keong, Chen, Jianbin, Yeong, Joe Poh Sheng, Wilm, Andreas, Amer, Lidyana Bte, Chang, Mei Mei, Gogna, Apoorva, Tan, Eng-Huat, Ng, Poh Yong, Wang, Lanying, Lim, Tony Kiat Hon, Yang, Hechuan, Skanderup, Anders Jacobsen

2020

Overview

Lung cancer is the world’s leading cause of cancer death and shows strong ancestry disparities. By sequencing and assembling a large genomic and transcriptomic dataset of lung adenocarcinoma (LUAD) in individuals of East Asian ancestry (EAS; n  = 305), we found that East Asian LUADs had more stable genomes characterized by fewer mutations and fewer copy number alterations than LUADs from individuals of European ancestry. This difference is much stronger in smokers as compared to nonsmokers. Transcriptomic clustering identified a new EAS-specific LUAD subgroup with a less complex genomic profile and upregulated immune-related genes, allowing the possibility of immunotherapy-based approaches. Integrative analysis across clinical and molecular features showed the importance of molecular phenotypes in patient prognostic stratification. EAS LUADs had better prediction accuracy than those of European ancestry, potentially due to their less complex genomic architecture. This study elucidated a comprehensive genomic landscape of EAS LUADs and highlighted important ancestry differences between the two cohorts. Genomic and transcriptomic analysis of lung adenocarcinoma (LUAD) in Asia indicates that Asian LUADs have fewer mutations, lower driver prevalence and fewer copy number alterations than European LUADs.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 14/35 / 38 / 38/39 / 38/91 / 45 / 45/23 / 631/114/2164 / 631/208/212 / 631/67/1612/1350 / 692/699/67/1612/1350 / Adenocarcinoma / Adenocarcinoma of Lung - etiology / Adenocarcinoma of Lung - genetics / Adenocarcinoma of Lung - mortality / Adenocarcinoma of Lung - therapy / Aged / Agriculture / Animal Genetics and Genomics / Asian Continental Ancestry Group - genetics / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Cohort Studies / Comparative analysis / DNA Copy Number Variations / ErbB Receptors - genetics / Exome / Female / Gene Expression Profiling / Gene Function / Genes / Genetic aspects / Genomes / Genomics / Health aspects / Human Genetics / Humans / Immunotherapy / Lung cancer / Lung Neoplasms - etiology / Lung Neoplasms - genetics / Lung Neoplasms - mortality / Lung Neoplasms - therapy / Male / Medical colleges / Middle Aged / Mutation / Proto-Oncogene Proteins p21(ras) - genetics / Singapore / Smokers / Tumor Suppressor Protein p53 - genetics