Highly recurrent TERT promoter mutations in human melanoma.
Highly recurrent TERT promoter mutations in human melanoma.
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DOI：
10.1126/science.1229259
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发表时间：
2013-02-22
期刊：
影响因子：
--
通讯作者：
Garraway LA
中科院分区：
文献类型：
--
作者：
Huang FW;Hodis E;Xu MJ;Kryukov GV;Chin L;Garraway LA
测序研究已经在人类癌症基因中发现了许多复发性编码突变；然而，涉及调控区域的高复发性突变很少被观察到。在这里，我们描述了TERT核心启动子内的两个独立突变，当它们结合在一起时，在71%（70个中的50个）黑色素瘤中观察到，并产生了新的一致的ETS结合基序。报告分析显示，这些突变使TERT启动子的转录活性增加了2 - 4倍。对来自不同肿瘤类型的癌细胞系的检查显示，16%（150例中的24例）的病例中有相同的突变，初步证据表明，膀胱癌和肝癌细胞的频率升高。因此，基因组调控区域的体细胞突变可能是一个重要的致瘤机制。
Sequencing studies have identified many recurrent coding mutations in human cancer genes; however, highly recurrent mutations involving regulatory regions have rarely been observed. Here we describe two independent mutations within the TERT core promoter that, when taken together, were observed in 71% (50 of 70) of melanomas and generate de novo consensus ETS binding motifs. Reporter assays showed that these mutations increase transcriptional activity from the TERT promoter by 2–4-fold. Examination of cancer cell lines derived from diverse tumor types revealed the same mutations in 16% (24 of 150) of cases, with preliminary evidence of elevated frequency in bladder and hepatocellular cancer cells. Thus, somatic mutations in regulatory regions of the genome may represent an important tumorigenic mechanism.
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影响因子：
30.8
作者：
Krauthammer, Michael;Kong, Yong;Ha, Byung Hak;Evans, Perry;Bacchiocchi, Antonella;McCusker, James P.;Cheng, Elaine;Davis, Matthew J.;Goh, Gerald;Choi, Murim;Ariyan, Stephan;Narayan, Deepak;Dutton-Regester, Ken;Capatana, Ana;Holman, Edna C.;Bosenberg, Marcus;Sznol, Mario;Kluger, Harriet M.;Brash, Douglas E.;Stern, David F.;Materin, Miguel A.;Lo, Roger S.;Mane, Shrikant;Ma, Shuangge;Kidd, Kenneth K.;Hayward, Nicholas K.;Lifton, Richard P.;Schlessinger, Joseph;Boggon, Titus J.;Halaban, Ruth
通讯作者：
Halaban, Ruth
影响因子：
64.8
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
通讯作者：
Garraway, Levi A.
影响因子：
64.8
作者：
Barretina, Jordi;Caponigro, Giordano;Stransky, Nicolas;Venkatesan, Kavitha;Margolin, Adam A.;Kim, Sungjoon;Wilson, Christopher J.;Lehar, Joseph;Kryukov, Gregory V.;Sonkin, Dmitriy;Reddy, Anupama;Liu, Manway;Murray, Lauren;Berger, Michael F.;Monahan, John E.;Morais, Paula;Meltzer, Jodi;Korejwa, Adam;Jane-Valbuena, Judit;Mapa, Felipa A.;Thibault, Joseph;Bric-Furlong, Eva;Raman, Pichai;Shipway, Aaron;Engels, Ingo H.;Cheng, Jill;Yu, Guoying K.;Yu, Jianjun;Aspesi, Peter, Jr.;de Silva, Melanie;Jagtap, Kalpana;Jones, Michael D.;Wang, Li;Hatton, Charles;Palescandolo, Emanuele;Gupta, Supriya;Mahan, Scott;Sougnez, Carrie;Onofrio, Robert C.;Liefeld, Ted;MacConaill, Laura;Winckler, Wendy;Reich, Michael;Li, Nanxin;Mesirov, Jill P.;Gabriel, Stacey B.;Getz, Gad;Ardlie, Kristin;Chan, Vivien;Myer, Vic E.;Weber, Barbara L.;Porter, Jeff;Warmuth, Markus;Finan, Peter;Harris, Jennifer L.;Meyerson, Matthew;Golub, Todd R.;Morrissey, Michael P.;Sellers, William R.;Schlegel, Robert;Garraway, Levi A.
通讯作者：
Garraway, Levi A.
影响因子：
64.5
作者：
Hodis E;Watson IR;Kryukov GV;Arold ST;Imielinski M;Theurillat JP;Nickerson E;Auclair D;Li L;Place C;Dicara D;Ramos AH;Lawrence MS;Cibulskis K;Sivachenko A;Voet D;Saksena G;Stransky N;Onofrio RC;Winckler W;Ardlie K;Wagle N;Wargo J;Chong K;Morton DL;Stemke-Hale K;Chen G;Noble M;Meyerson M;Ladbury JE;Davies MA;Gershenwald JE;Wagner SN;Hoon DS;Schadendorf D;Lander ES;Gabriel SB;Getz G;Garraway LA;Chin L
通讯作者：
Chin L
影响因子：
64.8
作者：
Michaloglou, C;Vredeveld, LCW;Peeper, DS
通讯作者：
Peeper, DS