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

Adam J. Bass, Hideo Watanabe, Craig H. Mermel, Soyoung Yu, Sven Perner, Roel G. 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 KomisarofLucian 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 K. Marie, Olav Dahl, Ramesh A. Shivdasani, Ming Sound Tsao, Mark A. Rubin, Kwok K. Wong, Aviv Regev, William C. Hahn, David G. Beer, Anil K. Rustgi, Matthew Meyerson

Research output: Contribution to journalArticle

650 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1238-1242
Number of pages5
JournalNature genetics
Volume41
Issue number11
DOIs
StatePublished - Nov 1 2009

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas'. Together they form a unique fingerprint.

  • Cite this

    Bass, A. J., Watanabe, H., Mermel, C. H., Yu, S., Perner, S., Verhaak, R. G., Kim, S. Y., Wardwell, L., Tamayo, P., Gat-Viks, I., Ramos, A. H., Woo, M. S., Weir, B. A., Getz, G., Beroukhim, R., O'Kelly, M., Dutt, A., Rozenblatt-Rosen, O., Dziunycz, P., ... Meyerson, M. (2009). SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas. Nature genetics, 41(11), 1238-1242. https://doi.org/10.1038/ng.465