Genomic landscape of lung adenocarcinoma in East Asians

被引：370

作者：

Chen, Jianbin ^{[1
]}

Yang, Hechuan ^{[1
,2
]}

Teo, Audrey Su Min ^{[1
]}

Amer, Lidyana Bte ^{[1
]}

Sherbaf, Faranak Ghazi ^{[1
]}

Tan, Chu Quan ^{[1
]}

Alvarez, Jacob Josiah Santiago ^{[1
]}

Lu, Bingxin ^{[1
]}

Lim, Jia Qi ^{[1
]}

Takano, Angela ^{[3
]}

Nahar, Rahul ^{[1
]}

Lee, Yin Yeng ^{[1
]}

Phual, Cheryl Zi Jin ^{[1
]}

Chua, Khi Pin ^{[1
]}

Suteja, Lisda ^{[4
]}

Chen, Pauline Jieqi ^{[1
]}

Chang, Mei Mei ^{[1
]}

Koh, Tina Puay Theng ^{[5
]}

Ong, Boon-Hean ^{[6
]}

Anantham, Devanand ^{[7
]}

Hsu, Anne Ann Ling ^{[7
]}

Gogna, Apoorva ^{[8
]}

Too, Chow Wei ^{[8
]}

Aung, Zaw Win ^{[9
]}

Lee, Yi Fei ^{[1
,10
]}

Wang, Lanying ^{[9
]}

Lim, Tony Kiat Hon ^{[3
]}

Wilm, Andreas ^{[1
]}

Choi, Poh Sum ^{[1
]}

Ng, Poh Yong ^{[1
]}

Toh, Chee Keong ^{[4
]}

Lim, Wan-Teck ^{[4
,11
]}

Ma, Siming ^{[1
]}

Lim, Bing ^{[1
]}

Liu, Jin ^{[12
]}

Tam, Wai Leong ^{[1
,10
,13
,14
]}

Skanderup, Anders Jacobsen ^{[1
]}

Yeong, Joe Poh Sheng ^{[3
,11
]}

Tan, Eng-Huat ^{[4
,9
]}

Creasy, Caretha L. ^{[15
]}

Tan, Daniel Shao Weng ^{[1
,4
,16
]}

Hillmer, Axel M. ^{[1
,17
,18
]}

Zhai, Weiwei ^{[1
,2
,10
,19
]}

机构：

[1] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore

[2] Chinese Acad Sci, Inst Zool, Key Lab Zool Systemat & Evolut, Beijing, Peoples R China

[3] Singapore Gen Hosp, Dept Anat Pathol, Singapore, Singapore

[4] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore

[5] Natl Canc Ctr Singapore, Surg Oncol, Singapore, Singapore

[6] Natl Heart Ctr Singapore, Dept Cardiothorac Surg, Singapore, Singapore

[7] Singapore Gen Hosp, Dept Resp & Crit Care Med, Singapore, Singapore

[8] Singapore Gen Hosp, Dept Vasc & Intervent Radiol, Singapore, Singapore

[9] Natl Canc Ctr Singapore, Div Clin Trials & Epidemiol Sci, Singapore, Singapore

[10] Nanyang Technol Univ, Sch Biol Sci, Singapore, Singapore

[11] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Singapore, Singapore

[12] Duke NUS Med Sch, Ctr Quantitat Med, Program Hlth Serv & Syst Res, Singapore, Singapore

[13] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore

[14] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore, Singapore

[15] GlaxoSmithKline, Oncol R&D, Collegeville, PA USA

[16] Natl Canc Ctr Singapore, Div Med Sci, Canc Therapeut Res Lab, Singapore, Singapore

[17] Univ Cologne, Fac Med, Inst Pathol, Cologne, Germany

[18] Univ Cologne, Univ Hosp Cologne, Cologne, Germany

[19] Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming, Yunnan, Peoples R China

来源：

NATURE GENETICS | 2020年 / 52卷 / 02期

基金：

新加坡国家研究基金会; 美国国家科学基金会; 国家重点研发计划; 英国医学研究理事会;

关键词：

CANCER RISK; THERAPEUTIC TARGETS; MUTATIONS; EXPRESSION; DIVERSITY; HETEROGENEITY; MEN; DISCOVERY; FRAMEWORK; PATHWAYS;

D O I：

10.1038/s41588-019-0569-6

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：177 / +

页数：23

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