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Nat Commun. 2014 Mar 27;5:3518. doi: 10.1038/ncomms4518.

Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids.

Author information

1
Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, University of Cologne, 50924 Cologne, Germany.
2
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
3
Computational Molecular Biology Group, Max Planck Institute for Molecular Genetics, D-14195 Berlin, Germany.
4
Department of Pathology, University Hospital Medical Center, University of Cologne, 50937 Cologne, Germany.
5
Laboratory of Translational Cancer Genomics, Center of Integrated Oncology Cologne - Bonn, University of Cologne, 50924 Cologne, Germany.
6
Department I of Internal Medicine, Center of Integrated Oncology Kö ln-Bonn, University of Cologne, 50924 Cologne, Germany.
7
Network Genomic Medicine, University Hospital Cologne, Center of Integrated Oncology Cologne Bonn, 50924 Cologne, Germany.
8
Cologne Center for Genomics (CCG), University of Cologne, Cologne, 50931 Germany.
9
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
10
Institute of Human Genetics, University of Cologne, Cologne 50931, Germany.
11
Computing Center, University of Cologne, 50931 Cologne, Germany.
12
Department of Informatics, University of Cologne, 50931 Cologne, Germany.
13
Institute of Legal Medicine, University of Cologne, 50823 Cologne, Germany.
14
Institute for Surgical Pathology, University Hospital Zurich, 8091 Zurich, Switzerland.
15
Institute of clinical medicine, Faculty of Medicine, University of Oslo, N-0424 Oslo, Norway.
16
Department of oncology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway.
17
Department of Thoracic Surgery, Rikshospitalet, Oslo University Hospital, N-0027 Oslo, Norway.
18
Department of pathology, Norwegian Radium Hospital, Oslo University Hospital, N-0310 Oslo, Norway.
19
Thoracic Surgery, Lungenklinik Merheim, Kliniken der Stadt Köln gGmbH, 51109 Cologne, Germany.
20
University of Melbourne Department of Surgery, St Vincent's Hospital, Melbourne, 3065 Victoria, Australia.
21
Department of Pathology, St. Vincent's Hospital, Melbourne, 3065 Victoria, Australia.
22
Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, 3002 Victoria, Australia.
23
Roy Castle Lung Cancer Research Programme, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool Cancer Research Centre, Liverpool, L3 9TA, UK.
24
Institute of Pathology, Jena University Hospital, Friedrich-Schiller-University, 07743 Jena, Germany.
25
Department of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, 53127 Bonn, Germany.
26
Vanderbilt-Ingram Cancer Center, Nashville, TN37232, USA.
27
Department of Medical Oncology, Istituto Toscano Tumouri, 57100 Livorno, Italy.
28
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York 10065, USA.
29
Department of Pathology, CHU Grenoble INSERM U823, Institute Albert Bonniot 38043 CS10217 Grenoble, France.
#
Contributed equally

Abstract

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.

PMID:
24670920
PMCID:
PMC4132974
DOI:
10.1038/ncomms4518
[Indexed for MEDLINE]
Free PMC Article

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