SOX2 is an amplified lineage-survival oncogene in lung and esophageal squamous cell carcinomas.
Publication/Presentation Date
11-1-2009
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.
Volume
41
Issue
11
First Page
1238
Last Page
1242
ISSN
1546-1718
Published In/Presented At
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., Komisarof, J., … 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
Disciplines
Medicine and Health Sciences
PubMedID
19801978
Department(s)
Hematology-Medical Oncology Division
Document Type
Article