Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids

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Item Type:	Article
Title:	Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids
Creators Name:	Fernandez-Cuesta, L., Peifer, M., Lu, X., Sun, R., Ozretić, L., Seidal, D., Zander, T., Leenders, F., George, J., Müller, C., Dahmen, I., Pinther, B., Bosco, G., Konrad, K., Altmüller, J., Nürnberg, P., Achter, V., Lang, U., Schneider, P.M., Bogus, M., Soltermann, A., Brustugun, O.T., Helland, Å., Solberg, S., Lund-Iversen, M., Ansén, S., Stoelben, E., Wright, G.M., Russell, P., Wainer, Z., Solomon, B., Field, J.K., Hyde, R., Davies, M.P., Heukamp, L.C., Petersen, I., Perner, S., Lovly, C., Cappuzzo, F., Travis, W.D., Wolf, J., Vingron, M., Brambilla, E., Haas, S.A., Buettner, R. and Thomas, R.K.
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.
Keywords:	Base Sequence, Carcinoid Tumor, Chromatin Assembly and Disassembly, Chromosome Mapping, DNA Copy Number Variations, DNA Sequence Analysis, Exome, Gene Expression Profiling, Gene Dosage, Human Genome, Lung Neoplasms, Molecular Sequence Data, Mutation, Neoplastic Gene Expression Regulation, Single Nucleotide Polymorphism, Young Adult
Source:	Nature Communications
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	5
Page Range:	3518
Date:	27 March 2014
Official Publication:	https://doi.org/10.1038/ncomms4518
PubMed:	View item in PubMed

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