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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Bass, AJ; Watanabe, H; Mermel, CH; Yu, S; Perner, S; Verhaak, RG; Kim, SY; Wardwell, L; Tamayo, P; Gat-Viks, I; Ramos, AH; Woo, MS; Weir, BA; Getz, G; Beroukhim, R; O'Kelly, M; Dutt, A; Rozenblatt-Rosen, O; Dziunycz, P; Komisarof, J; Chirieac, LR; Lafargue, CJ; Scheble, V; Wilbertz, T; Ma, C; Rao, S; Nakagawa, H; Stairs, DB; Lin, L; Giordano, TJ; Wagner, P; Minna, JD; Gazdar, AF; Zhu, CQ; Brose, MS; Cecconello, I; Ribeiro, U; Marie, SK; Dahl, O; Shivdasani, RA; Tsao, M-S; Rubin, MA; Wong, KK; Regev, A; Hahn, WC; Beer, DG; Rustgi, AK; Meyerson, M

Published Date

  • November 2009

Published In

Volume / Issue

  • 41 / 11

Start / End Page

  • 1238 - 1242

PubMed ID

  • 19801978

Pubmed Central ID

  • 19801978

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.465

Language

  • eng