Somatic mutations affect key pathways in lung adenocarcinoma.
Somatic mutations affect key pathways in lung adenocarcinoma.
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DOI：
10.1038/nature07423
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发表时间：
2008-10-23
期刊：
影响因子：
64.8
通讯作者：
Wilson, Richard K.
中科院分区：
文献类型：
--
作者：
Ding, Li;Getz, Gad;Wheeler, David A.;Mardis, Elaine R.;McLellan, Michael D.;Cibulskis, Kristian;Sougnez, Carrie;Greulich, Heidi;Muzny, Donna M.;Morgan, Margaret B.;Fulton, Lucinda;Fulton, Robert S.;Zhang, Qunyuan;Wendl, Michael C.;Lawrence, Michael S.;Larson, David E.;Chen, Ken;Dooling, David J.;Sabo, Aniko;Hawes, Alicia C.;Shen, Hua;Jhangiani, Shalini N.;Lewis, Lora R.;Hall, Otis;Zhu, Yiming;Mathew, Tittu;Ren, Yanru;Yao, Jiqiang;Scherer, Steven E.;Clerc, Kerstin;Metcalf, Ginger A.;Ng, Brian;Milosavljevic, Aleksandar;Gonzalez-Garay, Manuel L.;Osborne, John R.;Meyer, Rick;Shi, Xiaoqi;Tang, Yuzhu;Koboldt, Daniel C.;Lin, Ling;Abbott, Rachel;Miner, Tracie L.;Pohl, Craig;Fewell, Ginger;Haipek, Carrie;Schmidt, Heather;Dunford-Shore, Brian H.;Kraja, Aldi;Crosby, Seth D.;Sawyer, Christopher S.;Vickery, Tammi;Sander, Sacha;Robinson, Jody;Winckler, Wendy;Baldwin, Jennifer;Chirieac, Lucian R.;Dutt, Amit;Fennell, Tim;Hanna, Megan;Johnson, Bruce E.;Onofrio, Robert C.;Thomas, Roman K.;Tonon, Giovanni;Weir, Barbara A.;Zhao, Xiaojun;Ziaugra, Liuda;Zody, Michael C.;Giordano, Thomas;Orringer, Mark B.;Roth, Jack A.;Spitz, Margaret R.;Wistuba, Ignacio I.;Ozenberger, Bradley;Good, Peter J.;Chang, Andrew C.;Beer, David G.;Watson, Mark A.;Ladanyi, Marc;Broderick, Stephen;Yoshizawa, Akihiko;Travis, William D.;Pao, William;Province, Michael A.;Weinstock, George M.;Varmus, Harold E.;Gabriel, Stacey B.;Lander, Eric S.;Gibbs, Richard A.;Meyerson, Matthew;Wilson, Richard K.
确定癌症的遗传基础需要对大量组织病理学分类良好的原发肿瘤进行综合分析。在这里，我们报告了一项发现188人肺腺癌体细胞突变的合作研究的结果。对623个已知或潜在与癌症相关的基因进行的DNA测序显示，样本中有1000多个体细胞突变。我们的分析确定了26个突变频率很高的基因，因此可能与致癌有关。经常发生突变的基因包括酪氨酸激酶，其中包括EGFR同系物ERBB4；多种ephrin受体基因，尤其是EPHA3；血管内皮生长因子受体；和NTRK基因。这些数据为原发性肺腺癌中涉及其他癌症的几种肿瘤抑制基因（包括NF1、APC、RB1和atm）的体细胞突变以及PTPRD和经常被删除的基因LRP1B的序列变化提供了证据。观察到的突变谱与临床特征、吸烟状况和DNA修复缺陷相关。这些结果被包括单核苷酸多态性阵列和基因表达阵列在内的数据整合所加强。我们的发现进一步揭示了与肺腺癌相关的几个重要信号通路，并提出了新的治疗分子靶点。
Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers—including NF1, APC, RB1 and ATM—and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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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：
64.5
作者：
CAWTHON, RM;WEISS, R;WHITE, R
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WHITE, R
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11.2
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Le Calvez, F;Mukeria, A;Hainaut, P
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Marchetti, Antonio;Felicioni, Lara;Buttitta, Fianuna
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Buttitta, Fianuna
影响因子：
158.5
作者：
Kobayashi, S;Boggon, TJ;Halmos, B
通讯作者：
Halmos, B