Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.

Nat Commun 2014 Mar 27;5:3518. Epub 2014 Mar 27.

Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.

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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http://dx.doi.org/10.1038/ncomms4518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132974PMC
March 2014
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