Letter abstract


Nature Genetics 41, 1238 - 1242 (2009)
Published online: 4 October 2009 | doi:10.1038/ng.465

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

Adam J Bass1,4,18, Hideo Watanabe1,3,4,18, Craig H Mermel1,3,4, Soyoung Yu1,3, Sven Perner5,6, Roel G Verhaak1,3,4, So Young Kim1,3, Leslie Wardwell1,3, Pablo Tamayo4, Irit Gat-Viks4, Alex H Ramos1,3,4, Michele S Woo1,3,4, Barbara A Weir1,3,4, Gad Getz4, Rameen Beroukhim1,4, Michael O'Kelly4, Amit Dutt1,3,4, Orit Rozenblatt-Rosen1,3, Piotr Dziunycz1, Justin Komisarof1, Lucian R Chirieac7, Christopher J LaFargue5, Veit Scheble6, Theresia Wilbertz6, Changqing Ma8, Shilpa Rao8, Hiroshi Nakagawa8,9, Douglas B Stairs8,9, Lin Lin10, Thomas J Giordano11, Patrick Wagner5, John D Minna12, Adi F Gazdar12, Chang Qi Zhu13, Marcia S Brose8,14, Ivan Cecconello15, Ulysses Ribeiro Jr15, Suely K Marie15, Olav Dahl16, Ramesh A Shivdasani1,2, Ming-Sound Tsao13, Mark A Rubin5, Kwok K Wong1,2, Aviv Regev4, William C Hahn1,4, David G Beer10, Anil K Rustgi8,9,17 & Matthew Meyerson1,3,4,7


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.

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  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  2. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
  3. Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  4. Broad Institute, Cambridge, Massachusetts, USA.
  5. Department of Pathology, Weill Medical College of Cornell University, New York, New York, USA.
  6. Institute of Pathology, Comprehensive Cancer Center, University Hospitals of Tuebingen, Tuebingen, Germany.
  7. Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
  8. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  9. Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  10. Section of Thoracic Surgery, Department of Surgery, Ann Arbor, Michigan, USA.
  11. Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
  12. University of Texas Southwestern Medical Center, Dallas, Texas, USA.
  13. University Health Network and Princess Margaret Hospital, Toronto, Canada.
  14. Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  15. School of Medicine, University of São Paolo, São Paolo, Brazil.
  16. Section of Oncology, University of Bergen, Bergen, Norway.
  17. Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  18. These authors contributed equally to this work.

Correspondence to: Matthew Meyerson1,3,4,7
e-mail: matthew_meyerson@dfci.harvard.edu



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