Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids

被引：260

作者：

Fernandez-Cuesta, Lynnette ^{[1
]}

Peifer, Martin ^{[1
,2
]}

Lu, Xin ^{[1
]}

Sun, Ruping ^{[3
]}

Ozretic, Luka ^{[4
]}

Seidel, Danila ^{[1
,5
]}

Zander, Thomas ^{[1
,6
,7
]}

Leenders, Frauke ^{[1
,5
]}

George, Julie ^{[1
]}

Mueller, Christian ^{[1
]}

Dahmen, Ilona ^{[1
]}

Pinther, Berit ^{[1
]}

Bosco, Graziella ^{[1
]}

Konrad, Kathryn ^{[8
]}

Altmueller, Janine ^{[8
,9
,10
]}

Nuernberg, Peter ^{[2
,8
,9
]}

Achter, Viktor ^{[11
]}

Lang, Ulrich ^{[11
,12
]}

Schneider, Peter M. ^{[13
]}

Bogus, Magdalena ^{[13
]}

Soltermann, Alex ^{[14
]}

Brustugun, Odd Terje ^{[15
,16
]}

Helland, Aslaug ^{[15
,16
]}

Solberg, Steinar ^{[17
]}

Lund-Iversen, Marius ^{[18
]}

Ansen, Sascha ^{[6
]}

Stoelben, Erich ^{[19
]}

Wright, Gavin M. ^{[20
]}

Russell, Prudence ^{[21
]}

Wainer, Zoe ^{[20
]}

Solomon, Benjamin ^{[22
]}

Field, John K. ^{[23
]}

Hyde, Russell ^{[23
]}

Davies, Michael P. A. ^{[23
]}

Heukamp, Lukas C. ^{[4
,7
]}

Petersen, Iver ^{[24
]}

Perner, Sven ^{[25
]}

Lovly, Christine M. ^{[26
]}

Cappuzzo, Federico ^{[27
]}

Travis, William D. ^{[28
]}

Wolf, Juergen ^{[5
,6
,7
]}

Vingron, Martin ^{[3
]}

Brambilla, Elisabeth ^{[29
]}

Haas, Stefan A. ^{[3
]}

Buettner, Reinhard ^{[4
,5
,7
]}

Thomas, Roman K. ^{[1
,4
,5
]}

机构：

[1] Univ Cologne, Fac Med, Ctr Integrated Oncol Cologne Bonn, Dept Translat Genom, D-50924 Cologne, Germany

[2] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany

[3] Max Planck Inst Mol Genet, Computat Mol Biol Grp, D-14195 Berlin, Germany

[4] Univ Cologne, Univ Hosp Med Ctr, Dept Pathol, D-50937 Cologne, Germany

[5] Univ Cologne, Ctr Integrated Oncol Cologne Bonn, Lab Translat Canc Genom, D-50924 Cologne, Germany

[6] Univ Cologne, Ctr Integrated Oncol Koln Bonn, Dept Internal Med, D-50924 Cologne, Germany

[7] Univ Hosp Cologne, Ctr Integrated Oncol Cologne Bonn, Network Genom Med, D-50924 Cologne, Germany

[8] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany

[9] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany

[10] Univ Cologne, Inst Human Genet, D-50931 Cologne, Germany

[11] Univ Cologne, Ctr Comp, D-50931 Cologne, Germany

[12] Univ Cologne, Dept Informat, D-50931 Cologne, Germany

[13] Univ Cologne, Inst Legal Med, D-50823 Cologne, Germany

[14] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland

[15] Univ Oslo, Fac Med, Inst Clin Med, N-0424 Oslo, Norway

[16] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Oncol, N-0310 Oslo, Norway

[17] Oslo Univ Hosp, Rikshosp, Dept Thorac Surg, N-0027 Oslo, Norway

[18] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Pathol, N-0310 Oslo, Norway

[19] Kliniken Stadt Koln gGmbH, Lungenklin Merheim, D-51109 Cologne, Germany

[20] Univ Melbourne, St Vincents Hosp, Dept Surg, Melbourne, Vic 3065, Australia

[21] St Vincents Hosp, Dept Pathol, Melbourne, Vic 3065, Australia

[22] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic 3002, Australia

[23] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Dept Mol & Clin Canc Med,Inst Translat Med, Liverpool L3 9TA, Merseyside, England

[24] Univ Jena, Jena Univ Hosp, Inst Pathol, D-07743 Jena, Germany

[25] Univ Hosp Bonn, Inst Pathol, Dept Prostate Canc Res, D-53127 Bonn, Germany

[26] Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

[27] Ist Toscano Tumouri, Dept Med Oncol, I-57100 Livorno, Italy

[28] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10065 USA

[29] CHU Grenoble, Inst Albert Bonniot, INSERM U823, Dept Pathol, F-38043 Grenoble, France

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

关键词：

CLASS DISCOVERY; COMPLEX; EXPRESSION; CANCER; DECAY;

D O I：

10.1038/ncomms4518

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：7

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