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Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids
Pulmonary carcinoids are rare neuroendocrine tumors of the lung. The molecular alterations underlying the pathogenesis of these tumors have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary c...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132974/ https://www.ncbi.nlm.nih.gov/pubmed/24670920 http://dx.doi.org/10.1038/ncomms4518 |
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author | Fernandez-Cuesta, Lynnette Peifer, Martin Lu, Xin Sun, Ruping Ozretić, Luka Seidal, Danila Zander, Thomas Leenders, Frauke George, Julie Müller, Christian Dahmen, Ilona Pinther, Berit Bosco, Graziella Konrad, Kathryn Altmüller, Janine Nürnberg, Peter Achter, Viktor Lang, Ulrich Schneider, Peter M Bogus, Magdalena Soltermann, Alex Brustugun, Odd Terje Helland, Åslaug Solberg, Steinar Lund-Iversen, Marius Ansén, Sascha Stoelben, Erich Wright, Gavin M. Russell, Prudence Wainer, Zoe Solomon, Benjamin Field, John K Hyde, Russell Davies, Michael PA. Heukamp, Lukas C Petersen, Iver Perner, Sven Lovly, Christine Cappuzzo, Federico Travis, William D Wolf, Jürgen Vingron, Martin Brambilla, Elisabeth Haas, Stefan A. Buettner, Reinhard Thomas, Roman K |
author_facet | Fernandez-Cuesta, Lynnette Peifer, Martin Lu, Xin Sun, Ruping Ozretić, Luka Seidal, Danila Zander, Thomas Leenders, Frauke George, Julie Müller, Christian Dahmen, Ilona Pinther, Berit Bosco, Graziella Konrad, Kathryn Altmüller, Janine Nürnberg, Peter Achter, Viktor Lang, Ulrich Schneider, Peter M Bogus, Magdalena Soltermann, Alex Brustugun, Odd Terje Helland, Åslaug Solberg, Steinar Lund-Iversen, Marius Ansén, Sascha Stoelben, Erich Wright, Gavin M. Russell, Prudence Wainer, Zoe Solomon, Benjamin Field, John K Hyde, Russell Davies, Michael PA. Heukamp, Lukas C Petersen, Iver Perner, Sven Lovly, Christine Cappuzzo, Federico Travis, William D Wolf, Jürgen Vingron, Martin Brambilla, Elisabeth Haas, Stefan A. Buettner, Reinhard Thomas, Roman K |
author_sort | Fernandez-Cuesta, Lynnette |
collection | PubMed |
description | Pulmonary carcinoids are rare neuroendocrine tumors of the lung. The molecular alterations underlying the pathogenesis of these tumors have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodeling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40% and 22.2% of the cases respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine tumors, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumors but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin remodeling genes is sufficient to drive transformation in pulmonary carcinoids. |
format | Online Article Text |
id | pubmed-4132974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-41329742014-09-27 Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids Fernandez-Cuesta, Lynnette Peifer, Martin Lu, Xin Sun, Ruping Ozretić, Luka Seidal, Danila Zander, Thomas Leenders, Frauke George, Julie Müller, Christian Dahmen, Ilona Pinther, Berit Bosco, Graziella Konrad, Kathryn Altmüller, Janine Nürnberg, Peter Achter, Viktor Lang, Ulrich Schneider, Peter M Bogus, Magdalena Soltermann, Alex Brustugun, Odd Terje Helland, Åslaug Solberg, Steinar Lund-Iversen, Marius Ansén, Sascha Stoelben, Erich Wright, Gavin M. Russell, Prudence Wainer, Zoe Solomon, Benjamin Field, John K Hyde, Russell Davies, Michael PA. Heukamp, Lukas C Petersen, Iver Perner, Sven Lovly, Christine Cappuzzo, Federico Travis, William D Wolf, Jürgen Vingron, Martin Brambilla, Elisabeth Haas, Stefan A. Buettner, Reinhard Thomas, Roman K Nat Commun Article Pulmonary carcinoids are rare neuroendocrine tumors of the lung. The molecular alterations underlying the pathogenesis of these tumors have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodeling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40% and 22.2% of the cases respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine tumors, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumors but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin remodeling genes is sufficient to drive transformation in pulmonary carcinoids. 2014-03-27 /pmc/articles/PMC4132974/ /pubmed/24670920 http://dx.doi.org/10.1038/ncomms4518 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Fernandez-Cuesta, Lynnette Peifer, Martin Lu, Xin Sun, Ruping Ozretić, Luka Seidal, Danila Zander, Thomas Leenders, Frauke George, Julie Müller, Christian Dahmen, Ilona Pinther, Berit Bosco, Graziella Konrad, Kathryn Altmüller, Janine Nürnberg, Peter Achter, Viktor Lang, Ulrich Schneider, Peter M Bogus, Magdalena Soltermann, Alex Brustugun, Odd Terje Helland, Åslaug Solberg, Steinar Lund-Iversen, Marius Ansén, Sascha Stoelben, Erich Wright, Gavin M. Russell, Prudence Wainer, Zoe Solomon, Benjamin Field, John K Hyde, Russell Davies, Michael PA. Heukamp, Lukas C Petersen, Iver Perner, Sven Lovly, Christine Cappuzzo, Federico Travis, William D Wolf, Jürgen Vingron, Martin Brambilla, Elisabeth Haas, Stefan A. Buettner, Reinhard Thomas, Roman K Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids |
title | Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids |
title_full | Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids |
title_fullStr | Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids |
title_full_unstemmed | Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids |
title_short | Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids |
title_sort | frequent mutations in chromatin-remodeling genes in pulmonary carcinoids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132974/ https://www.ncbi.nlm.nih.gov/pubmed/24670920 http://dx.doi.org/10.1038/ncomms4518 |
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