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SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas

2009; Nature Portfolio; Volume: 41; Issue: 11 Linguagem: Inglês

10.1038/ng.465

1546-1718

Adam J. Bass, Hideo Watanabe, Craig H. Mermel, Soyoung Yu, Sven Perner, Roel G.W. Verhaak, So Young Kim, Leslie Wardwell, Pablo Tamayo, Irit Gat‐Viks, Alex H. Ramos, Michele S. Woo, Barbara A. Weir, Gad Getz, Rameen Beroukhim, Michael O'Kelly, Amit Dutt, Orit Rozenblatt–Rosen, Piotr Dziunycz, Justin Komisarof, Lucian R. Chirieac, Christopher J. Lafargue, Veit Scheble, Theresia Wilbertz, Changqing Ma, Shilpa Rao, Hiroshi Nakagawa, Douglas B. Stairs, Lin Lin, Thomas J. Giordano, Patrick Wagner, John D. Minna, Adi F. Gazdar, Chang‐Qi Zhu, Marcia S. Brose, Ivan Cecconello, Ulysses Ribeiro, Suely Kazue Nagahashi Marie, Olav Dahl, Ramesh A. Shivdasani, Ming‐Sound Tsao, Mark A. Rubin, Kwok‐Kin Wong, Aviv Regev, William C. Hahn, David G. Beer, Anil K. Rustgi, Matthew Meyerson,

Renal and related cancers

Matthew Meyerson and colleagues report that SOX2, which encodes a transcription factor necessary for normal esophageal development, is an amplified lineage survival oncogene in lung and esophageal squamous cell carcinomas. 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 development1,2. 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 malformations3, is necessary for normal esophageal squamous development4, promotes differentiation and proliferation of basal tracheal cells5 and cooperates in induction of pluripotent stem cells6,7,8. 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 here 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 characteristics identify SOX2 as a lineage-survival oncogene in lung and esophageal SCC.