BGI-Shenzhen, Shenzhen, People's Republic of China.
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
J Thorac Oncol. 2016 Dec;11(12):2129-2140. doi: 10.1016/j.jtho.2016.08.142. Epub 2016 Sep 9.
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.
肺腺癌（LUAD）是肺癌的主要组织学亚型，其发病率在亚洲人群中较高，尤其在女性非吸烟者中更为显著。亚洲人群 LUAD 的突变模式可能与白人 LUAD 的突变模式不同。
我们对 271 例切除的 LUAD 肿瘤（主要为 I 期）进行了分析，以确定亚洲人群 LUAD 的基因组特征，重点关注女性非吸烟者。
EGFR、KRAS、erb-b2 受体酪氨酸激酶 2 基因（ERBB2）和 BRAF 的突变；涉及间变性淋巴瘤受体酪氨酸激酶基因（ALK）、ROS1 和 ret 原癌基因（RET）的基因融合；以及 Met 原癌基因酪氨酸激酶（MET）外显子 14 跳跃是亚洲人群 LUAD 的主要驱动因素，它们与非亚洲人群 LUAD 研究报道的驱动因素相互排斥且存在不同的流行率。此外，我们还发现了一种新的突变特征 XNX（在中间位置的突变碱基 N 两侧是 5' 和 3' 位置上的两个相同碱基），在非吸烟者的 LUAD 肿瘤中过度表达，与总体突变频率呈负相关。
在本队列中，约 85%的个体具有已知的驱动突变（EGFR 59.4%、KRAS 7.4%、ALK 7.4%、ERBB2 2.6%、ROS1 2.2%、RET 2.2%、MET 1.8%、BRAF 1.1%和 NRAS 0.4%）。70%的吸烟者和 90%的不吸烟者有明确的致癌驱动因素，与美国食品和药物管理局批准的靶向治疗相匹配。
