Chen, J., Yang, H., Teo, A.S.M. et al. Genomic landscape of lung adenocarcinoma in East Asians. Nat Genet 52, 177–186 (2020). https://doi.org/10.1038/s41588-019-0569-6
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.
This work was funded by Glaxo Wellcome Manufacturing PTE LTD and Agency for Science, Technology and Research (A*STAR) (GIS/15-IAF100) and supported by the Lung Cancer Consortium Singapore (LCCS) and the National Medical Research Council (Singapore) through the Translational and Clinical Research Program (NMRC/TCR/007-NCC/2013). LCCS is jointly supported by philanthropy (Singapore Millenium Foundation, etc.), institutional and industrial grants. W.Z is supported in part by the National Key R&D program of China grant 2018YFC0910400 and 2018YFC1406902. We thank Beijing Genomics Institute for providing the published sequencing data. We thank Chin Thing Jo Ong, Yen Ling Lee, Ivan Ming Lai Chua and Wendy Wei Jia Soon for next generation sequencing work, GIS Research Pipeline Development team for support on analysis pipelines, Yasuji Matsuoka for administrative support. We thank Dr Lee May Ann of the Experimental Therapeutics Centre, A*STAR, Singapore for providing the ETCC016 (RRID: CVCL_Y086) cell line. We thank
Prof Cun Yupeng for helpful discussions.