肺类癌中染色质重塑基因的频繁突变。
Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.
作者信息
Fernandez-Cuesta Lynnette, Peifer Martin, Lu Xin, Sun Ruping, Ozretić Luka, Seidal Danila, Zander Thomas, Leenders Frauke, George Julie, Müller Christian, Dahmen Ilona, Pinther Berit, Bosco Graziella, Konrad Kathryn, Altmüller Janine, Nürnberg Peter, Achter Viktor, Lang Ulrich, Schneider Peter M, Bogus Magdalena, Soltermann Alex, Brustugun Odd Terje, Helland Åslaug, Solberg Steinar, Lund-Iversen Marius, Ansén Sascha, Stoelben Erich, Wright Gavin M, Russell Prudence, Wainer Zoe, Solomon Benjamin, Field John K, Hyde Russell, Davies Michael Pa, Heukamp Lukas C, Petersen Iver, Perner Sven, Lovly Christine, Cappuzzo Federico, Travis William D, Wolf Jürgen, Vingron Martin, Brambilla Elisabeth, Haas Stefan A, Buettner Reinhard, Thomas Roman K
机构信息
Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
出版信息
Nat Commun. 2014 Mar 27;5:3518. doi: 10.1038/ncomms4518.
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.
肺类癌是一种罕见的肺神经内分泌肿瘤。迄今为止，尚未对这些肿瘤发病机制的分子改变进行系统研究。在此，我们对肺类癌进行了基因拷贝数分析（n = 54）、基因组/外显子组（n = 44）和转录组（n = 69）测序，并观察到染色质重塑基因频繁发生突变。分别有40%和22.2%的病例中，共价组蛋白修饰因子和SWI/SNF复合物的亚基发生突变，MEN1、PSIP1和ARID1A经常受到影响。与小细胞肺癌和大细胞神经内分泌肺肿瘤不同，TP53和RB1突变是罕见事件，这表明肺类癌不是高侵袭性肺神经内分泌肿瘤的早期祖细胞病变，而是通过独立的细胞机制产生。这些数据还表明，染色质重塑基因的失活足以驱动肺类癌的转化。
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