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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.

Pubmed ID: 19801978

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
  • Jr UR
  • Marie SK
  • Dahl O
  • Shivdasani RA
  • Tsao MS
  • Rubin MA
  • Wong KK
  • Regev A
  • Hahn WC
  • Beer DG
  • Rustgi AK
  • Meyerson M

Journal

Nature genetics

Publication Data

November 28, 2009

Associated Grants

  • Agency: NCI NIH HHS, Id: 5P01CA098101-05
  • Agency: NIH HHS, Id: DP1 OD003958
  • Agency: NCI NIH HHS, Id: K08 CA134931
  • Agency: NCI NIH HHS, Id: K08 CA134931-01
  • Agency: NCI NIH HHS, Id: K08CA134931
  • Agency: NCI NIH HHS, Id: P01 CA098101
  • Agency: NCI NIH HHS, Id: P01 CA098101-01A1
  • Agency: NCI NIH HHS, Id: P01CA098101-05
  • Agency: NCI NIH HHS, Id: P30 CA016520
  • Agency: NCI NIH HHS, Id: P50 CA070907
  • Agency: NCI NIH HHS, Id: P50 CA070907-029001
  • Agency: NCI NIH HHS, Id: P50 CA090578
  • Agency: NCI NIH HHS, Id: P50 CA090578-069005
  • Agency: NCI NIH HHS, Id: P50CA70907
  • Agency: NCI NIH HHS, Id: P50CA90578
  • Agency: NCI NIH HHS, Id: R01 CA071606
  • Agency: NCI NIH HHS, Id: R01 CA071606-12
  • Agency: NCI NIH HHS, Id: R01 CA109038
  • Agency: NCI NIH HHS, Id: R01 CA109038-04
  • Agency: NCI NIH HHS, Id: R01 CA154365
  • Agency: NCI NIH HHS, Id: R01CA071606-12
  • Agency: NCI NIH HHS, Id: R01CA109038
  • Agency: NCI NIH HHS, Id: R33 CA128625
  • Agency: NCI NIH HHS, Id: R33 CA128625-01A1
  • Agency: NCI NIH HHS, Id: R33CA128625
  • Agency: NIGMS NIH HHS, Id: T32 GM007753

Mesh Terms

  • Carcinoma, Squamous Cell
  • Cell Differentiation
  • Cell Lineage
  • Cell Survival
  • Esophageal Neoplasms
  • Gene Amplification
  • Genome, Human
  • Humans
  • Lung Neoplasms
  • Oncogenes
  • RNA Interference
  • SOXB1 Transcription Factors