Frequent mutations in chromatin-remodeling genes in pulmonary carcinoids
نویسندگان
چکیده
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.
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Lynnette Fernandez-Cuesta1,*, Martin Peifer1,2,*, Xin Lu1, Ruping Sun3, Luka Ozretić4, Danila Seidel1,5, Thomas Zander1,6,7, Frauke Leenders1,5, Julie George1, Christian Müller1, Ilona Dahmen1, Berit Pinther1, Graziella Bosco1, Kathryn Konrad8, Janine Altmüller8,9,10, Peter Nürnberg2,8,9, Viktor Achter11, Ulrich Lang11,12, Peter M. Schneider13, Magdalena Bogus13, Alex Soltermann14, Odd Terje Br...
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