Journal Article

Genomic landscape of lung adenocarcinoma in East Asians

Teo, Audrey Su Min, Nahar, Rahul, Chua, Khi Pin, Phua, Cheryl Zi Jin, Aung, Zaw Win, Takano, Angela, Lee, Yi Fei, Choi, Poh Sum, Alvarez, Jacob Josiah Santiago, Lim, Tony Kia Thon, Ong, Boon-Hean, Hillmer, Axel M, Sherbaf, Faranak Ghazi, Zhai, Weiwei, Lee, Yin Yeng, Tam, Wai Leong, Hsu, Anne Ann Ling, Creasy, Caretha L, Wei, Chow, Lu, Bingxin, Tan, Daniel Shao Weng, Koh, Tina Puay Theng, Liu, Jin, Qi Lim, Jia, 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, 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.

• Publisher: Nature Publishing Group
• Subject: Adenocarcinoma / Age / Clustering / Copy number / Gene expression / Genomes / Genomics / Immunotherapy / Lung cancer / Mutation / Patients / Phenotypes / Smoking / Subgroups / Tumorigenesis