Ha Sang Yun, Choi So-Jung, Cho Jong Ho, Choi Hye Joo, Lee Jinseon, Jung Kyungsoo, Irwin Darry, Liu Xiao, Lira Maruja E, Mao Mao, Kim Hong Kwan, Choi Yong Soo, Shim Young Mog, Park Woong Yang, Choi Yoon-La, Kim Jhingook
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Oncotarget. 2015 Mar 10;6(7):5465-74. doi: 10.18632/oncotarget.2925.
The aim of this study was to determine the distribution of known oncogenic driver mutations in female never-smoker Asian patients with lung adenocarcinoma. We analyzed 214 mutations across 26 lung cancer-associated genes and three fusion genes using the MassARRAY LungCarta Panel and the ALK, ROS1, and RET fusion assays in 198 consecutively resected lung adenocarcinomas from never-smoker females at a single institution. EGFR mutation, which was the most frequent driver gene mutation, was detected in 124 (63%) cases. Mutation of ALK, KRAS, PIK3CA, ERBB2, BRAF, ROS1, and RET genesoccurred in 7%, 4%, 2.5%, 1.5%, 1%, 1%, and 1% of cases, respectively. Thus, 79% of lung adenocarcinomas from never-smoker females harbored well-known oncogenic mutations. Mucinous adenocarcinomas tended to have a lower frequency of known driver gene mutations than other histologic subtypes. EGFR mutation was associated with older age and a predominantly acinar pattern, while ALK rearrangement was associated with younger age and a predominantly solid pattern. Lung cancer in never-smoker Asian females is a distinct entity, with the majority of these cancers developing from oncogenic mutations.
本研究旨在确定从不吸烟的亚洲女性肺腺癌患者中已知致癌驱动基因突变的分布情况。我们使用MassARRAY LungCarta Panel以及ALK、ROS1和RET融合检测法，对来自单一机构的198例连续切除的从不吸烟女性肺腺癌患者的26个肺癌相关基因和3个融合基因中的214个突变进行了分析。最常见的驱动基因突变是EGFR突变，在124例（63%）患者中检测到。ALK、KRAS、PIK3CA、ERBB2、BRAF、ROS1和RET基因的突变分别发生在7%、4%、2.5%、1.5%、1%、1%和1%的病例中。因此，从不吸烟女性的肺腺癌中，79%存在已知的致癌突变。黏液腺癌的已知驱动基因突变频率往往低于其他组织学亚型。EGFR突变与年龄较大和主要为腺泡型有关，而ALK重排与年龄较小和主要为实体型有关。从不吸烟的亚洲女性肺癌是一种独特的疾病实体，这些癌症大多由致癌突变发展而来。
