Genomic landscape of non-small cell lung cancer in smokers and never-smokers.
Genomic landscape of non-small cell lung cancer in smokers and never-smokers.
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DOI：
10.1016/j.cell.2012.08.024
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发表时间：
2012-09-14
期刊：
影响因子：
64.5
通讯作者：
Wilson RK
中科院分区：
文献类型：
--
作者：
Govindan R;Ding L;Griffith M;Subramanian J;Dees ND;Kanchi KL;Maher CA;Fulton R;Fulton L;Wallis J;Chen K;Walker J;McDonald S;Bose R;Ornitz D;Xiong D;You M;Dooling DJ;Watson M;Mardis ER;Wilson RK
我们报告了17例非小细胞肺癌（NSCLC）患者的肿瘤和邻近正常组织样本的全基因组和转录组测序结果。我们在编码序列中发现了3，726个点突变和90多个indel，吸烟者的平均突变频率比从不吸烟者高出10倍以上。与DACH 1、CFTR、ABCB 5和HGF相关的染色体修饰和DNA修复途径的基因中的新改变被鉴定为沿着。深度数字测序揭示了从不吸烟者和吸烟者的不同克隆模式。所有经验证的EFGR和KRAS突变均存在于创始克隆中，表明在癌症起始中可能的作用。分析显示了14种融合，包括ROS 1和ALK以及新的代谢酶。细胞周期和JAK-STAT通路在肺癌中显著改变，沿着54个基因的扰动，这些基因可能是目前可用药物的靶向基因。
We report the results of whole genome and transcriptome sequencing of tumor and adjacent normal tissue samples from 17 patients with non-small cell lung carcinoma (NSCLC). We identified 3,726 point mutations and over 90 indels in the coding sequence, with an average mutation frequency more than 10-fold higher in smokers than in never-smokers. Novel alterations in genes involved in chromatic modification and DNA repair pathways were identified along with DACH1, CFTR, RELN, ABCB5, and HGF. Deep digital sequencing revealed diverse clonality patterns in both never smokers and smokers. All validated EFGR and KRAS mutations were present in the founder clones, suggesting possible roles in cancer initiation. Analysis revealed 14 fusions including ROS1 and ALK as well as novel metabolic enzymes. Cell cycle and JAK-STAT pathways are significantly altered in lung cancer along with perturbations in 54 genes that are potentially targetable with currently available drugs.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
影响因子：
14.9
作者：
Kanehisa M;Goto S;Sato Y;Furumichi M;Tanabe M
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Tanabe M
影响因子：
82.9
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Kohno T;Ichikawa H;Totoki Y;Yasuda K;Hiramoto M;Nammo T;Sakamoto H;Tsuta K;Furuta K;Shimada Y;Iwakawa R;Ogiwara H;Oike T;Enari M;Schetter AJ;Okayama H;Haugen A;Skaug V;Chiku S;Yamanaka I;Arai Y;Watanabe S;Sekine I;Ogawa S;Harris CC;Tsuda H;Yoshida T;Yokota J;Shibata T
通讯作者：
Shibata T
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Gu TL;Deng X;Huang F;Tucker M;Crosby K;Rimkunas V;Wang Y;Deng G;Zhu L;Tan Z;Hu Y;Wu C;Nardone J;MacNeill J;Ren J;Reeves C;Innocenti G;Norris B;Yuan J;Yu J;Haack H;Shen B;Peng C;Li H;Zhou X;Liu X;Rush J;Comb MJ
通讯作者：
Comb MJ