Fernandez-Cuesta, Lynnette ORCID: 0000-0002-0724-6703, Peifer, Martin ORCID: 0000-0002-5243-5503, Lu, Xin, Sun, Ruping, Ozretic, Luka, Seidel, Danila ORCID: 0000-0003-4388-3117, Zander, Thomas, Leenders, Frauke, George, Julie, Mueller, Christian, Dahmen, Ilona, Pinther, Berit, Bosco, Graziella, Konrad, Kathryn, Altmueller, Janine, Nuernberg, Peter, Achter, Viktor, Lang, Ulrich ORCID: 0000-0001-7166-0805, Schneider, Peter M. ORCID: 0000-0003-0744-2349, Bogus, Magdalena, Soltermann, Alex, Brustugun, Odd Terje, Helland, Aslaug ORCID: 0000-0002-5520-0275, Solberg, Steinar, Lund-Iversen, Marius, Ansen, Sascha, Stoelben, Erich, Wright, Gavin M., Russell, Prudence, Wainer, Zoe, Solomon, Benjamin, Field, John K. ORCID: 0000-0003-3951-6365, Hyde, Russell, Davies, Michael P. A., Heukamp, Lukas C., Petersen, Iver, Perner, Sven, Lovly, Christine M., Cappuzzo, Federico, Travis, William D., Wolf, Juergen, Vingron, Martin, Brambilla, Elisabeth, Haas, Stefan A., Buettner, Reinhard and Thomas, Roman K. (2014). Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids. Nat. Commun., 5. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours 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-remodelling 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 lung tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumours but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin-remodelling genes is sufficient to drive transformation in pulmonary carcinoids.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fernandez-Cuesta, LynnetteUNSPECIFIEDorcid.org/0000-0002-0724-6703UNSPECIFIED
Peifer, MartinUNSPECIFIEDorcid.org/0000-0002-5243-5503UNSPECIFIED
Lu, XinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sun, RupingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ozretic, LukaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidel, DanilaUNSPECIFIEDorcid.org/0000-0003-4388-3117UNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leenders, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
George, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dahmen, IlonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pinther, BeritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bosco, GraziellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konrad, KathrynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Achter, ViktorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, UlrichUNSPECIFIEDorcid.org/0000-0001-7166-0805UNSPECIFIED
Schneider, Peter M.UNSPECIFIEDorcid.org/0000-0003-0744-2349UNSPECIFIED
Bogus, MagdalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soltermann, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brustugun, Odd TerjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helland, AslaugUNSPECIFIEDorcid.org/0000-0002-5520-0275UNSPECIFIED
Solberg, SteinarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lund-Iversen, MariusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ansen, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoelben, ErichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wright, Gavin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Russell, PrudenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wainer, ZoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solomon, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Field, John K.UNSPECIFIEDorcid.org/0000-0003-3951-6365UNSPECIFIED
Hyde, RussellUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davies, Michael P. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heukamp, Lukas C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petersen, IverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perner, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lovly, Christine M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cappuzzo, FedericoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Travis, William D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vingron, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brambilla, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haas, Stefan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-445503
DOI: 10.1038/ncomms4518
Journal or Publication Title: Nat. Commun.
Volume: 5
Date: 2014
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Mathematics and Computer Science > Institute of Computer Science
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CLASS DISCOVERY; COMPLEX; EXPRESSION; CANCER; DECAYMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/44550

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