Xu Ziguang, Li Hongxia, Dong Yujie, Cheng Peng, Luo Fang, Fu Shijun, Gao Min, Kong Lingfei, Che Nanying
Department of Pathology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China.
Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing, People's Republic of China.
Onco Targets Ther. 2020 Jun 30;13:6245-6253. doi: 10.2147/OTT.S241231. eCollection 2020.
Mesenchymal-epithelial transition () exon14 skipping mutations represent a clinically unique molecular subtype of NSCLC. The prevalence rates of exon 14 skipping in lung adenocarcinoma (ADC) range from 0.9% to 4.0% in Asian populations. Since some somatic variants that do not encompass the exon 14 splice sites might also induce exon 14 skipping, the RNA-based sequencing is speculated as the most accurate method for detecting exon 14 skipping.
A total of 951 NSCLC patients from two hospitals were enrolled in this study. exon14 skipping was detected using RNA-based next-generation sequencing (NGS). Also, immunohistochemistry (IHC) was performed in 405 samples simultaneously.
The overall estimated prevalence of exon 14 skipping was approximately 1.8% in ADCs and 1.7% in NSCLCs. The detection rate of exon 14 skipping from surgical resection specimen was 2.3% in NSCLCs and 2.0% in ADCs. The exon 14 skipping was identified in 6.6% of ////-negative ADCs. Additionally, PD-L1 was found to be highly expressed in NSCLC patients harboring exon 14 skipping (<0.01).
The prevalence of exon14 skipping in lung ADCs in the East Asian population was similar to that of the Western population as assessed by RNA-based NGS. The NSCLC patients with exon 14 skipping were older than those with other oncogenic driver mutations, such as , and . In addition, PD-L1 was highly expressed in NSCLC patients with exon 14 skipping.
间充质-上皮转化（MET）外显子14跳跃突变代表非小细胞肺癌（NSCLC）临床上独特的分子亚型。在亚洲人群中，肺腺癌（ADC）中外显子14跳跃的发生率在0.9%至4.0%之间。由于一些不包含MET外显子14剪接位点的体细胞变异也可能诱导MET外显子14跳跃，基于RNA的测序被推测为检测外显子14跳跃最准确的方法。
本研究纳入了来自两家医院的951例NSCLC患者。使用基于RNA的下一代测序（NGS）检测MET外显子14跳跃。此外，同时对405份样本进行了免疫组织化学（IHC）检测。
ADC中MET外显子14跳跃的总体估计发生率约为1.8%，NSCLC中为1.7%。手术切除标本中MET外显子14跳跃的检出率在NSCLC中为2.3%，在ADC中为2.0%。在////阴性的ADC中，6.6%检测到MET外显子14跳跃。此外，发现MET外显子14跳跃的NSCLC患者中PD-L1高表达（<0.01）。
通过基于RNA的NGS评估，东亚人群肺ADC中MET外显子14跳跃的发生率与西方人群相似。MET外显子14跳跃的NSCLC患者比携带其他致癌驱动突变（如、和）的患者年龄更大。此外，MET外显子14跳跃的NSCLC患者中PD-L1高表达。
