Exome sequencing identifies somatic mutations in novel driver genes in non-small cell lung cancer
Exome sequencing identifies somatic mutations in novel driver genes in non-small cell lung cancer
复制标题
外显子组测序鉴定非小细胞肺癌新型驱动基因的体细胞突变
DOI：
10.18632/aging.103500
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发表时间：
2020-07-15
期刊：
影响因子：
5.2
通讯作者：
Zheng, Cuixia
中科院分区：
文献类型：
--
作者：
Zhang, Manman;Zhang, Lele;Zheng, Cuixia
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，在非小细胞肺癌（NSCLC）中探索新的驱动基因突变具有重要的临床意义。通过初步的生物信息学分析，我们在13例NSCLC患者中发现了体细胞基因突变，并在88例患者的扩展验证组中通过靶向测序证实了这些突变。在UNC5D（7.9%）、PREX1（5.0%）、HECW1（4.0%）、DACH1（2.0%）和GPC5（2.0%）中检测到复发突变。对UNC5D突变体也进行了功能研究。UNC5D的突变通过消除编码蛋白的肿瘤抑制功能来促进肿瘤发生。此外，在10例肺鳞状细胞癌患者中，我们发现KEAP1/NFE2L2突变在体内和体外影响靶基因的表达。总的来说，我们的研究结果扩大了参与NSCLC发病机制的驱动突变的已知谱。
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 UNC5D (7.9%), PREX1 (5.0%), HECW1 (4.0%), DACH1 (2.0%), and GPC5 (2.0%). A functional study was also performed in UNC5D mutants. Mutations in UNC5D 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 KEAP1/NFE2L2 that influenced the expression of target genes in vivo and in vitro. Overall, the results of our study expanded the known spectrum of driver mutations involved in the pathogenesis of NSCLC.