Genomic landscape of lung adenocarcinoma in East Asians

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 sta...

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Published inNature genetics Vol. 52; no. 2; pp. 177 - 3
Main Authors Chen, Jianbin, Yang, Hechuan, Teo, Audrey Su Min, Amer, Lidyana Bte, Sherbaf, Faranak Ghazi, Tan, Chu Quan, Alvarez, Jacob Josiah Santiago, Lu, Bingxin, Qi Lim, Jia, Takano, Angela, Nahar, Rahul, Lee, Yin Yeng, Phua, Cheryl Zi Jin, Chua, Khi Pin, Suteja, Lisda, Chen, Pauline Jieqi, Chang, Mei Mei, Koh, Tina Puay Theng, Ong, Boon-Hean, Anantham, Devanand, Hsu, Anne Ann Ling, Gogna, Apoorva, Wei, Chow, Aung, Zaw Win, Lee, Yi Fei, Wang, Lanying, Lim, Tony Kia Thon, Wilm, Andreas, Choi, Poh Sum, Ng, Poh Yong, Toh, Chee Keong, Lim, Wan-Teck, Ma, Siming, Lim, Bing, Liu, Jin, Tam, Wai Leong, Skanderup, Anders Jacobsen, Yeong, Joe Poh Sheng, Tan, Eng-Huat, Creasy, Caretha L, Tan, Daniel Shao Weng, Hillmer, Axel M, Zhai, Weiwei
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group 01.02.2020
Subjects
Adenocarcinoma
Age
Clustering
Copy number
Gene expression
Genomes
Genomics
Immunotherapy
Lung cancer
Mutation
Patients
Phenotypes
Smoking
Subgroups
Tumorigenesis
Singapore
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Summary: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.
ISSN:1061-4036
1546-1718
DOI:10.1038/s41588-019-0567-6