Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma.
Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma.
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基因组测序确定 ELF3 是壶腹癌的驱动因素。
DOI：
10.1016/j.ccell.2015.12.012
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发表时间：
2016-02-08
期刊：
影响因子：
50.3
通讯作者：
Shibata T
中科院分区：
文献类型：
--
作者：
Yachida S;Wood LD;Suzuki M;Takai E;Totoki Y;Kato M;Luchini C;Arai Y;Nakamura H;Hama N;Elzawahry A;Hosoda F;Shirota T;Morimoto N;Hori K;Funazaki J;Tanaka H;Morizane C;Okusaka T;Nara S;Shimada K;Hiraoka N;Taniguchi H;Higuchi R;Oshima M;Okano K;Hirono S;Mizuma M;Arihiro K;Yamamoto M;Unno M;Yamaue H;Weiss MJ;Wolfgang CL;Furukawa T;Nakagama H;Vogelstein B;Kiyono T;Hruban RH;Shibata T
壶腹癌是高度恶性的肿瘤，可以有肠或胰胆分化。为了表征壶腹癌的体细胞改变，我们对60例壶腹癌进行了全外显子组测序和DNA拷贝数分析，这些壶腹癌是从临床特征良好的日本和美国患者中切除的。接下来，我们选择了92个基因并进行了靶向测序，以验证另外112种癌症中的显著突变基因。具有肠表型的癌中驱动基因突变的发生率与具有胰胆表型的癌不同。我们鉴定了特征性显著突变的驱动基因（ELF3）以及先前已知的驱动基因（TP53、KRAS、APC等）。功能研究表明，正常人上皮细胞中的ELF3沉默增强了它们的运动性和侵袭性。
Ampullary carcinomas are highly malignant neoplasms that can have either intestinal or pancreatobiliary differentiation. To characterize somatic alterations in ampullary carcinomas, we performed whole-exome sequencing and DNA copy number analysis on 60 ampullary carcinomas resected from clinically well-characterized Japanese and American patients. We next selected 92 genes and performed targeted-sequencing to validate significantly mutated genes in additional 112 cancers. The prevalence of driver gene mutations in carcinomas with the intestinal phenotype is different from those with the pancreatobiliary phenotype. We identified a characteristic significantly mutated driver gene (ELF3) as well as previously known driver genes (TP53, KRAS, APC and others). Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances their motility and invasion.
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DOI：
10.1073/pnas.0710052104
发表时间：
2007-12-11
影响因子：
11.1
作者：
Beroukhim, Rameen;Getz, Gad;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
2.5
作者：
Okano, Keiichi;Oshima, Minoru;Suzuki, Yasuyuki
通讯作者：
Suzuki, Yasuyuki
影响因子：
4.7
作者：
Herter-Sprie GS;Greulich H;Wong KK
通讯作者：
Wong KK
影响因子：
8.8
作者：
Fedorenko, I. V.;Gibney, G. T.;Sondak, V. K.;Smalley, K. S. M.
通讯作者：
Smalley, K. S. M.
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.