Dhanasekaran Saravana M, Balbin O Alejandro, Chen Guoan, Nadal Ernest, Kalyana-Sundaram Shanker, Pan Jincheng, Veeneman Brendan, Cao Xuhong, Malik Rohit, Vats Pankaj, Wang Rui, Huang Stephanie, Zhong Jinjie, Jing Xiaojun, Iyer Matthew, Wu Yi-Mi, Harms Paul W, Lin Jules, Reddy Rishindra, Brennan Christine, Palanisamy Nallasivam, Chang Andrew C, Truini Anna, Truini Mauro, Robinson Dan R, Beer David G, Chinnaiyan Arul M
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2] Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [3].
1] Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2].
Nat Commun. 2014 Dec 22;5:5893. doi: 10.1038/ncomms6893.
Lung cancer is emerging as a paradigm for disease molecular subtyping, facilitating targeted therapy based on driving somatic alterations. Here we perform transcriptome analysis of 153 samples representing lung adenocarcinomas, squamous cell carcinomas, large cell lung cancer, adenoid cystic carcinomas and cell lines. By integrating our data with The Cancer Genome Atlas and published sources, we analyse 753 lung cancer samples for gene fusions and other transcriptomic alterations. We show that higher numbers of gene fusions is an independent prognostic factor for poor survival in lung cancer. Our analysis confirms the recently reported CD74-NRG1 fusion and suggests that NRG1, NF1 and Hippo pathway fusions may play important roles in tumours without known driver mutations. In addition, we observe exon-skipping events in c-MET, which are attributable to splice site mutations. These classes of genetic aberrations may play a significant role in the genesis of lung cancers lacking known driver mutations.
肺癌正成为疾病分子亚型分类的范例，推动基于驱动性体细胞改变的靶向治疗。在此，我们对153个样本进行了转录组分析，这些样本代表肺腺癌、肺鳞状细胞癌、大细胞肺癌、腺样囊性癌及细胞系。通过将我们的数据与癌症基因组图谱（The Cancer Genome Atlas）及已发表的数据来源相结合，我们分析了753个肺癌样本的基因融合及其他转录组改变。我们发现，基因融合数量较多是肺癌患者生存预后不良的一个独立预后因素。我们的分析证实了最近报道的CD74-NRG1融合，并提示NRG1、NF1和Hippo信号通路融合可能在无已知驱动突变的肿瘤中发挥重要作用。此外，我们在c-MET中观察到外显子跳跃事件，这归因于剪接位点突变。这些类型的基因畸变可能在缺乏已知驱动突变的肺癌发生过程中起重要作用。
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