Genomic landscape of lung adenocarcinoma in East Asians
Genomic landscape of lung adenocarcinoma in East Asians
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DOI：
10.1038/s41588-019-0569-6
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发表时间：
2020-02-03
期刊：
影响因子：
30.8
通讯作者：
Zhai, Weiwei
中科院分区：
文献类型：
--
作者：
Chen, Jianbin;Yang, Hechuan;Zhai, Weiwei
肺癌是世界上癌症死亡的主要原因，并显示出强烈的血统差异。通过对东亚血统(EAS；n=305)的肺腺癌(LUAD)基因组和转录数据库进行测序和组装，我们发现东亚的LUAD比欧洲血统的LUAD具有更稳定的基因组，具有更少的突变和更少的拷贝数变化。与不吸烟的人相比，吸烟者的这种差异要明显得多。转录聚类发现了一个新的EAS特异性LUAD亚群，其基因组图谱不那么复杂，免疫相关基因上调，从而使基于免疫治疗的方法成为可能。对临床和分子特征的综合分析表明，分子表型在患者预后分层中的重要性。EAS LUAD的预测准确率高于欧洲血统的那些，可能是因为它们的基因组结构不那么复杂。本研究阐明了EAS LUAD的基因组图谱，并强调了两个队列之间的重要祖先差异。亚洲肺腺癌(LUAD)的基因组和转录分析表明，与欧洲LUAD相比，亚洲LUAD具有较少的突变、较低的驱动器患病率和较少的拷贝数变化。
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.