Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.


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.

DOI: 10.1038/ncomms4518

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@article{FernndezCuesta2014FrequentMI, title={Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.}, author={Lynnette Fern{\'a}ndez-Cuesta and Martin Peifer and Xin Lu and Ruping Sun and Luka Ozreti{\'c} and Danila Seidal and Thomas Zander and Frauke Leenders and Julie George and Christian P M{\"{u}ller and Ilona Dahmen and Berit Pinther and Graziella Bosco and Kathryn Konrad and Janine Altm{\"{u}ller and Peter N{\"{u}rnberg and Viktor Achter and Ulrich Lang and Peter M. Schneider and Magdalena Bogus and Alex Soltermann and Odd Terje Brustugun and {\AA}slaug Helland and Steinar K Solberg and Marius Lund-Iversen and Sascha Ans{\'e}n and Erich Stoelben and Gavin Michael Wright and Prudence Anne Russell and Zoe Wainer and Benjamin J. Solomon and John K. Field and Russell Hyde and Michael A. Davies and Lukas Heukamp and Iver Petersen and Sven Perner and Christine M. Lovly and Federico Cappuzzo and William D. Travis and J{\"{u}rgen Wolf and Martin Vingron and Elisabeth M Brambilla and Stefan A. Haas and Reinhard H Buettner and Roman K. Thomas}, journal={Nature communications}, year={2014}, volume={5}, pages={3518} }