Clinical Research Center, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Aging (Albany NY). 2020 Jul 6;12(13):13701-13715. doi: 10.18632/aging.103500.
Lung cancer is the leading cause of cancer death worldwide and accounts for more than one-third of all newly diagnosed cancer cases in China. Therefore, it is of great clinical significance to explore new driver gene mutations in non-small-cell lung cancer (NSCLC). Using an initial bioinformatic analysis, we identified somatic gene mutations in 13 patients with NSCLC and confirmed these mutations by targeted sequencing in an extended validation group of 88 patients. Recurrent mutations were detected in (7.9%), (5.0%), (4.0%), (2.0%), and (2.0%). A functional study was also performed in UNC5D mutants. Mutations in promoted tumorigenesis by abolishing the tumor suppressor function of the encoded protein. Additionally, in ten patients with lung squamous cell carcinoma, we identified mutations in that influenced the expression of target genes and . Overall, the results of our study expanded the known spectrum of driver mutations involved in the pathogenesis of NSCLC.
肺癌是全球癌症死亡的主要原因，占中国所有新诊断癌症病例的三分之一以上。因此，探索非小细胞肺癌（NSCLC）中的新驱动基因突变具有重要的临床意义。我们使用初始的生物信息学分析，在 13 名 NSCLC 患者中鉴定出体细胞基因突变，并在 88 名扩展验证组患者中通过靶向测序对这些突变进行了确认。在 （7.9%）、 （5.0%）、 （4.0%）、 （2.0%）和 （2.0%）中检测到了复发性突变。我们还对 UNC5D 突变体进行了功能研究。突变导致编码蛋白的肿瘤抑制功能丧失，从而促进了肿瘤的发生。此外，在 10 名肺鳞癌患者中，我们鉴定出了影响靶基因 和 表达的 突变。总的来说，我们的研究结果扩展了已知的涉及 NSCLC 发病机制的驱动基因突变谱。
