Comprehensive Characterization of Oncogenic Drivers in Asian Lung Adenocarcinoma.
The incidence rate of lung adenocarcinoma (LUAD), the predominant histological subtype of lung cancer, is elevated in Asians, particularly in female nonsmokers. The mutation patterns in LUAD in Asians might be distinct from those in LUAD in whites.



We profiled 271 resected LUAD tumors (mainly stage I) to characterize the genomic landscape of LUAD in Asians with a focus on female nonsmokers.



Mutations in EGFR, KRAS, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), and BRAF; gene fusions involving anaplastic lymphoma receptor tyrosine kinase gene (ALK), ROS1, and ret proto-oncogene (RET); and Met Proto-Oncogene Tyrosine Kinase (MET) exon 14 skipping were the major drivers in LUAD in Asians, exhibiting mutually exclusive and differing prevalence from those reported in studies of LUAD in non-Asians. In addition, we identified a novel mutational signature of XNX (the mutated base N in the middle flanked by two identical bases at the 5' and 3' positions) that was overrepresented in LUAD tumors in nonsmokers and negatively correlated with the overall mutational frequency.



In this cohort, approximately 85% of individuals have known driver mutations (EGFR 59.4%, KRAS 7.4%, ALK 7.4%, ERBB2 2.6%, ROS1 2.2%, RET 2.2%, MET 1.8%, BRAF 1.1%, and NRAS 0.4%). Seventy percent of smokers and 90% of nonsmokers had defined oncogenic drivers matching the U.S. Food and Drug Administration-approved targeted therapies.
BGI-Shenzhen, Shenzhen, People's Republic of China.
Shiyong
S
Li
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Yoon-La
YL
Choi
BGI-Shenzhen, Shenzhen, People's Republic of China.
Zhuolin
Z
Gong
BGI-Shenzhen, Shenzhen, People's Republic of China.
Xiao
X
Liu
Pfizer Oncology, San Diego, California.
Maruja
M
Lira
Pfizer Oncology, San Diego, California.
Zhengyan
Z
Kan
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Ensel
E
Oh
Eli Lilly and Company, Indianapolis, Indiana.
Jian
J
Wang
Eli Lilly and Company, Indianapolis, Indiana.
Jason C
JC
Ting
Eli Lilly and Company, Indianapolis, Indiana.
Xiangsheng
X
Ye
Eli Lilly and Company, Indianapolis, Indiana.
Christoph
C
Reinhart
Merck Research Laboratories, Boston, Massachusetts.
Xiaoqiao
X
Liu
Merck Research Laboratories, Boston, Massachusetts.
Yunfei
Y
Pei
Merck Research Laboratories, Boston, Massachusetts.
Wei
W
Zhou
Merck Research Laboratories, Boston, Massachusetts.
Ronghua
R
Chen
Shanghai Biochip Company, Shanghai, People's Republic of China.
Shijun
S
Fu
Shanghai Biochip Company, Shanghai, People's Republic of China.
Gang
G
Jin
BGI-Shenzhen, Shenzhen, People's Republic of China.
Awei
A
Jiang
Pfizer Oncology, San Diego, California.
Julio
J
Fernandez
Pfizer Oncology, San Diego, California.
James
J
Hardwick
Department of Thoracic and Cardiovascular Surgery, Chungnam National University School of Medicine, Daejun, Republic of Korea.
Min Woong
MW
Kang
Department of Thoracic and Cardiovascular Surgery, Pusan National University School of Medicine, Pusan, Republic of Korea.
Hoseok
H
I
BGI-Shenzhen, Shenzhen, People's Republic of China.
Hancheng
H
Zheng
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Jhingook
J
Kim
Pfizer Oncology, San Diego, California. Electronic address: mao_m@yahoo.com.
Mao
M
Mao
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D055815:Young Adult
Adenocarcinoma; Asian; Driver genes; Lung cancer