SOX2 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 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, is necessary for normal esophageal squamous development, promotes differentiation and proliferation of basal tracheal cells and cooperates 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 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.

DOI: 10.1038/ng.465

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@inproceedings{Bass2009SOX2IA, title={SOX2 Is an Amplified Lineage Survival Oncogene in Lung and Esophageal Squamous Cell Carcinomas}, author={Adam J. Bass and Hideo Watanabe and Craig H. Mermel and Soyoung Yu and Sven Perner and Roel G. Verhaak and So Young Kim and Leslie Wardwell and Pablo Tamayo and Irit Gat-Viks and Alex H. Ramos and Michele S. Woo and Barbara A. Weir and Gad Getz and Rameen Beroukhim and Michael O’Kelly and Amit Dutt and Orit Rozenblatt-Rosen and Piotr Dziunycz and Justin Komisarof and Lucian R. Chirieac and Christopher J. LaFargue and Veit Scheble and Theresia Wilbertz and Changqing Ma and Shilpa Rao and Hiroshi Nakagawa and Douglas B. Stairs and Lin Lin and Thomas J. Giordano and Patrick Wagner and John D. Minna and Adi F. Gazdar and Chang Qi Zhu and Marcia S. Brose and Ivan Cecconello and Ulysses Ribeiro and Suely K. Marie and Olav Dahl and Ramesh A. Shivdasani and Ming-Sound Tsao and Mark A. Rubin and Kwok K. Wong and Aviv Regev and William C. Hahn and David G. Beer and Anil K. Rustgi and Matthew Meyerson}, booktitle={Nature genetics}, year={2009} }