SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.

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 genomi...

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Autores principales: Thomas Hussenet, Soraya Dali, Julien Exinger, Ben Monga, Bernard Jost, Doulaye Dembelé, Nadine Martinet, Christelle Thibault, Joerg Huelsken, Elisabeth Brambilla, Stanislas du Manoir
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Publicado: Public Library of Science (PLoS) 2010
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Acceso en línea:https://doaj.org/article/a3b2ea6dd9484143b1b61997e717f532
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spelling oai:doaj.org-article:a3b2ea6dd9484143b1b61997e717f5322021-11-25T06:26:16ZSOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.1932-620310.1371/journal.pone.0008960https://doaj.org/article/a3b2ea6dd9484143b1b61997e717f5322010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20126410/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Squamous 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.Thomas HussenetSoraya DaliJulien ExingerBen MongaBernard JostDoulaye DembeléNadine MartinetChristelle ThibaultJoerg HuelskenElisabeth BrambillaStanislas du ManoirPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8960 (2010)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Thomas Hussenet
Soraya Dali
Julien Exinger
Ben Monga
Bernard Jost
Doulaye Dembelé
Nadine Martinet
Christelle Thibault
Joerg Huelsken
Elisabeth Brambilla
Stanislas du Manoir
SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
description 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.
format article
author Thomas Hussenet
Soraya Dali
Julien Exinger
Ben Monga
Bernard Jost
Doulaye Dembelé
Nadine Martinet
Christelle Thibault
Joerg Huelsken
Elisabeth Brambilla
Stanislas du Manoir
author_facet Thomas Hussenet
Soraya Dali
Julien Exinger
Ben Monga
Bernard Jost
Doulaye Dembelé
Nadine Martinet
Christelle Thibault
Joerg Huelsken
Elisabeth Brambilla
Stanislas du Manoir
author_sort Thomas Hussenet
title SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
title_short SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
title_full SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
title_fullStr SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
title_full_unstemmed SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
title_sort sox2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas.
publisher Public Library of Science (PLoS)
publishDate 2010
url https://doaj.org/article/a3b2ea6dd9484143b1b61997e717f532
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