SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas.
SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas.
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DOI：
10.1038/ng.465
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发表时间：
2009-11
期刊：
影响因子：
30.8
通讯作者：
Meyerson, Matthew
中科院分区：
文献类型：
--
作者：
Bass, Adam J.;Watanabe, Hideo;Mermel, Craig H.;Yu, Soyoung;Perner, Sven;Verhaak, Roel G.;Kim, So Young;Wardwell, Leslie;Tamayo, Pablo;Gat-Viks, Irit;Ramos, Alex H.;Woo, Michele S.;Weir, Barbara A.;Getz, Gad;Beroukhim, Rameen;O'Kelly, Michael;Dutt, Amit;Rozenblatt-Rosen, Orit;Dziunycz, Piotr;Komisarof, Justin;Chirieac, Lucian R.;LaFargue, Christopher J.;Scheble, Veit;Wilbertz, Theresia;Ma, Changqing;Rao, Shilpa;Nakagawa, Hiroshi;Stairs, Douglas B.;Lin, Lin;Giordano, Thomas J.;Wagner, Patrick;Minna, John D.;Gazdar, Adi F.;Zhu, Chang Qi;Brose, Marcia S.;Cecconello, Ivan;Ribeiro, Ulysses, Jr.;Marie, Suely K.;Dahl, Olav;Shivdasani, Ramesh A.;Tsao, Ming-Sound;Rubin, Mark A.;Wong, Kwok K.;Regev, Aviv;Hahn, William C.;Beer, David G.;Rustgi, Anil K.;Meyerson, Matthew
在由某些细胞谱系产生的癌症中，谱系存活癌基因会因体细胞DNA改变而被激活，这些基因在正常发育过程中在这些细胞谱系中发挥作用。在此我们表明，在肺和食管的鳞状细胞癌（SCC）中发现的3q26.33号染色体上的一个基因组扩增峰包含转录因子基因SOX2。该基因在人类遗传性食管畸形中发生突变，对正常食管鳞状细胞发育是必需的，可促进气管基底细胞的分化和增殖，并在诱导多能干细胞过程中起协同作用。如RNA干扰实验所示，SOX2的表达对肺和食管细胞系的增殖以及不依赖贴壁的生长是必需的。此外，SOX2的异位表达与FOXE1或FGFR2协同作用，使永生化的气管支气管上皮细胞发生转化。SOX2驱动的肿瘤显示出鳞状分化和多能性的标志物表达。这些观察结果确定SOX2是肺和食管鳞状细胞癌中一种新的谱系存活癌基因。
Lineage survival oncogenes are activated by somatic DNA alterations in cancers arising from the cell lineages in which these genes play a role in normal development. Here we show that a peak of genomic amplification on chromosome 3q26.33, found in squamous cell carcinomas (SCCs) of the lung and esophagus, contains the transcription factor gene SOX2—which is mutated in hereditary human esophageal malformations and necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and co-operates in induction of pluripotent stem cells. SOX2 expression is required for proliferation and anchorage-independent growth of lung and esophageal cell lines, as shown by RNA interference experiments. Furthermore, ectopic expression of SOX2 cooperated with FOXE1 or FGFR2 to transform immortalized tracheobronchial epithelial cells. SOX2-driven tumors show expression of markers of both squamous differentiation and pluripotency. These observations identify SOX2 as a novel lineage survival oncogene in lung and esophageal SCC.
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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：
30.8
作者：
Segal, E;Friedman, N;Regev, A
通讯作者：
Regev, A
影响因子：
8
作者：
Lundberg, AS;Randell, SH;Hahn, WC
通讯作者：
Hahn, WC
影响因子：
64.8
作者：
Ebert, Benjamin L.;Pretz, Jennifer;Bosco, Jocelyn;Chang, Cindy Y.;Tamayo, Pablo;Galili, Naomi;Raza, Azra;Root, David E.;Attar, Eyal;Ellis, Steven R.;Golub, Todd R.
通讯作者：
Golub, Todd R.
影响因子：
30.8
作者：
Gudmundsson, Julius;Sulem, Patrick;Gudbjartsson, Daniel F.;Jonasson, Jon G.;Sigurdsson, Asgeir;Bergthorsson, Jon T.;He, Huiling;Blondal, Thorarinn;Geller, Frank;Jakobsdottir, Margret;Magnusdottir, Droplaug N.;Matthiasdottir, Sigurborg;Stacey, Simon N.;Skarphedinsson, Oskar B.;Helgadottir, Hafdis;Li, Wei;Nagy, Rebecca;Aguillo, Esperanza;Faure, Eduardo;Prats, Enrique;Saez, Berta;Martinez, Mariano;Eyjolfsson, Gudmundur I.;Bjornsdottir, Unnur S.;Holm, Hilma;Kristjansson, Kristleifur;Frigge, Michael L.;Kristvinsson, Hoskuldur;Gulcher, Jeffrey R.;Jonsson, Thorvaldur;Rafnar, Thorunn;Hjartarsson, Hannes;Mayordomo, Jose I.;de la Chapelle, Albert;Hrafnkelsson, Jon;Thorsteinsdottir, Unnur;Kong, Augustine;Stefansson, Kari
通讯作者：
Stefansson, Kari