Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids

Lynnette Fernandez-Cuesta, Martin Peifer, Xin Lu, Ruping Sun, Luka Ozretić, Danila Seidel, Thomas Zander, Frauke Leenders, Julie George, Christian Müller, Ilona Dahmen, Berit Pinther, Graziella Bosco, Kathryn Konrad, Janine Altmüller, Peter Nürnberg, Viktor Achter, Ulrich Lang, Peter M. Schneider, Magdalena BogusAlex Soltermann, Odd T.erje Brustugun, Åslaug Helland, Steinar Solberg, Marius Lund-Iversen, Sascha Ansén, Erich Stoelben, Gavin M. Wright, Prudence Russell, Zoe Wainer, Benjamin Solomon, John K. Field, Russell Hyde, Michael P.A. Davies, Lukas C. Heukamp, Iver Petersen, Sven Perner, Christine M. Lovly, Federico Cappuzzo, William D. Travis, Jürgen Wolf, Martin Vingron, Elisabeth Brambilla, Stefan A. Haas, Reinhard Buettner, Roman K. Thomas

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

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.

Original languageEnglish
Article number3518
Pages (from-to)3518
Number of pages1
JournalNature Communications
Volume5
DOIs
StatePublished - 2014

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