Li Chenguang, Gao Zhibo, Li Fei, Li Xiangchun, Sun Yihua, Wang Mengyun, Li Dan, Wang Rui, Li Fuming, Fang Rong, Pan Yunjian, Luo Xiaoyang, He Jing, Zheng Liangtao, Xia Jufeng, Qiu Lixin, He Jun, Ye Ting, Zhang Ruoxin, He Minghui, Zhu Meiling, Hu Haichuan, Shi Tingyan, Zhou Xiaoyan, Sun Menghong, Tian Shilin, Zhou Yong, Wang Qiaoxiu, Chen Longyun, Yin Guangliang, Lu Jingya, Wu Renhua, Guo Guangwu, Li Yingrui, Hu Xueda, Li Lin, Wang Qin, Yin Ye, Feng Qiang, Wang Bin, Wang Hang, Wang Mingbang, Yang Xiaonan, Zhang Xiuqing, Yang Huanming, Jin Li, Wang Cun-Yu, Ji Hongbin, Chen Haiquan, Wang Jun, Wei Qingyi
Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Sci Rep. 2015 Oct 27;5:14237. doi: 10.1038/srep14237.
Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy.
肺鳞状细胞癌（SQCC）约占所有肺癌病例的30%。目前，对于中国患者中这种肺癌亚型的突变图谱了解有限。我们对100例肺鳞状细胞癌患者的样本进行了全外显子组测序以寻找体细胞突变，并在另外98个样本中进行了后续的靶向捕获测序以进行验证。我们鉴定出20个显著突变的基因，包括TP53、CDH10、NFE2L2和PTEN。在76%的测试肿瘤样本中，频繁突变基因的通路包括细胞间粘附/Wnt/ Hippo通路、21%的氧化应激反应通路以及36%的磷脂酰肌醇-3-OH激酶通路。染色质调节因子基因的突变频率较低。在功能试验中，我们观察到敲低CDH10会促进细胞增殖、软琼脂集落形成、细胞迁移和细胞侵袭，而CDH10的过表达则会抑制细胞增殖。中国患者肺鳞状细胞癌的这种突变图谱提高了我们目前对肺癌发生、早期诊断和个性化治疗的认识。
Zotero 插件
