title: SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
abstract: Squamous cell carcinoma (SCC) of the lung is a frequent and aggressive cancer type. Gene amplifications, a known activating mechanism of oncogenes, target the 3q26-qter region as one of the most frequently gained/amplified genomic sites in SCC of various types. Here, we used array comparative genomic hybridization to delineate the consensus region of 3q26.3 amplifications in lung SCC. Recurrent amplifications occur in 20% of lung SCC (136 tumors in total) and map to a core region of 2 Mb (Megabases) that encompasses SOX2, a transcription factor gene. Intense SOX2 immunostaining is frequent in nuclei of lung SCC, indicating potential active transcriptional regulation by SOX2. Analyses of the transcriptome of lung SCC, SOX2-overexpressing lung epithelial cells and embryonic stem cells (ESCs) reveal that SOX2 contributes to activate ESC-like phenotypes and provide clues pertaining to the deregulated genes involved in the malignant phenotype. In cell culture experiments, overexpression of SOX2 stimulates cellular migration and anchorage-independent growth while SOX2 knockdown impairs cell growth. Finally, SOX2 over-expression in non-tumorigenic human lung bronchial epithelial cells is tumorigenic in immunocompromised mice. These results indicate that the SOX2 transcription factor, a major regulator of stem cell function, is also an oncogene and a driver gene for the recurrent 3q26.33 amplifications in lung SCC.
authors.affiliation: Département Biologie du Cancer, Institut National de la Santé et de la Recherche Médicale, Institut de Génétique et de Biologie Moléculaire et Cellulaire, U964 Illkirch, France. hussenet@igbmc.fr
authors.forename: Thomas
authors.initials: T
authors.lastname: Hussenet
authors.forename: Soraya
authors.initials: S
authors.lastname: Dali
authors.forename: Julien
authors.initials: J
authors.lastname: Exinger
authors.forename: Ben
authors.initials: B
authors.lastname: Monga
authors.forename: Bernard
authors.initials: B
authors.lastname: Jost
authors.forename: Doulaye
authors.initials: D
authors.lastname: Dembelé
authors.forename: Nadine
authors.initials: N
authors.lastname: Martinet
authors.forename: Christelle
authors.initials: C
authors.lastname: Thibault
authors.forename: Joerg
authors.initials: J
authors.lastname: Huelsken
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brambilla
authors.forename: Stanislas
authors.initials: S
authors.lastname: du Manoir
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics*
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors