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Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

N. Alcala, N. Leblay, A. A. G. Gabriel, L. Mangiante, D. Hervas, T. Giffon, A. S. Sertier, A. Ferrari, J. Derks, A. Ghantous, T. M. Delhomme, A. Chabrier, C. Cuenin, B. Abedi-Ardekani, A. Boland, R. Olaso, V. Meyer, J. Altmuller, F. Calvez-Kelm, G. Durand, C. Voegele, S. Boyault, L. Moonen, N. Lemaitre, P. Lorimier, A. C. Toffart, A. Soltermann, J. H. Clement, J. Saenger, J. K. Field, M. Brevet, C. Blanc-Fournier, F. Galateau-Salle, N. Le Stang, P. A. Russell, G. Wright, G. Sozzi, U. Pastorino, S. Lacomme, J. M. Vignaud, V. Hofman, P. Hofman, O. T. Brustugun, M. Lund-Iversen, V. Thomas de Montpreville, L. A. Muscarella, P. Graziano, H. Popper, J. Stojsic, J. F. Deleuze, Z. Herceg, A. Viari, P. Nuernberg, G. Pelosi, A. M. C. Dingemans, M. Milione, L. Roz, L. Brcic, M. Volante, M. G. Papotti, C. Caux, J. Sandoval, H. Hernandez-Vargas, E. Brambilla, E. J. M. Speel, N. Girard, S. Lantuejoul, J. D. McKay, M. Foll and L. Fernandez-Cuesta ()
Additional contact information
N. Alcala: 150 Cours Albert Thomas
N. Leblay: 150 Cours Albert Thomas
A. A. G. Gabriel: 150 Cours Albert Thomas
L. Mangiante: 150 Cours Albert Thomas
D. Hervas: Avenida Fernando Abril Martorell, Torre 106 A 7planta
T. Giffon: 150 Cours Albert Thomas
A. S. Sertier: Centre Léon Bérard, 28 Rue Laennec
A. Ferrari: Centre Léon Bérard, 28 Rue Laennec
J. Derks: Maastricht University Medical Centre (MUMC), GROW School for Oncology and Developmental Biology, P.O. Box 5800
A. Ghantous: Section of Mechanisms of Carcinogenesis, 150 Cours Albert Thomas
T. M. Delhomme: 150 Cours Albert Thomas
A. Chabrier: 150 Cours Albert Thomas
C. Cuenin: Section of Mechanisms of Carcinogenesis, 150 Cours Albert Thomas
B. Abedi-Ardekani: 150 Cours Albert Thomas
A. Boland: Université Paris-Saclay, 2 rue Gaston Crémieux, CP 5706
R. Olaso: Université Paris-Saclay, 2 rue Gaston Crémieux, CP 5706
V. Meyer: Université Paris-Saclay, 2 rue Gaston Crémieux, CP 5706
J. Altmuller: University of Cologne, Weyertal 115
F. Calvez-Kelm: 150 Cours Albert Thomas
G. Durand: 150 Cours Albert Thomas
C. Voegele: 150 Cours Albert Thomas
S. Boyault: Cancer Genomic Platform, 28 Rue Laennec
L. Moonen: Maastricht University Medical Centre (MUMC), GROW School for Oncology and Developmental Biology, P.O. Box 5800
N. Lemaitre: Site Santé, Allée des Alpes
P. Lorimier: Site Santé, Allée des Alpes
A. C. Toffart: Grenoble Alpes University Hospital
A. Soltermann: University Hospital Zurich, Schmelzbergstrasse 12
J. H. Clement: Jena University Hospital, Am Klinikum 1
J. Saenger: Bad Berka Institute of Pathology, Robert-Koch-Allee 9
J. K. Field: University of Liverpool, 6 West Derby Street
M. Brevet: University Claude Bernard Lyon 1, 59 Boulevard Pinel
C. Blanc-Fournier: CLCC François Baclesse, 3 avenue du Général Harris
F. Galateau-Salle: Centre Léon Bérard, 28, rue Laennec
N. Le Stang: Centre Léon Bérard, 28, rue Laennec
P. A. Russell: St. Vincent’s Hospital and University of Melbourne, Victoria Parade, Fitzroy
G. Wright: St. Vincent’s Hospital and University of Melbourne, Victoria Parade, Fitzroy
G. Sozzi: IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1
U. Pastorino: IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1
S. Lacomme: 29 Avenue du Maréchal de Lattre de Tassigny
J. M. Vignaud: 29 Avenue du Maréchal de Lattre de Tassigny
V. Hofman: Nice Hospital, Biobank BB-0033-00025, IRCAN Inserm U1081 CNRS 7284, University Côte d’Azur, 30 avenue de la voie Romaine, CS
P. Hofman: Nice Hospital, Biobank BB-0033-00025, IRCAN Inserm U1081 CNRS 7284, University Côte d’Azur, 30 avenue de la voie Romaine, CS
O. T. Brustugun: Vestre Viken HF, Postboks 800
M. Lund-Iversen: Oslo University Hospital, Ullernchausseen 70
V. Thomas de Montpreville: Marie Lannelongue Hospital, 133 avenue de la Resistance
L. A. Muscarella: Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1
P. Graziano: Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini 1
H. Popper: Medical University of Graz, Neue Stiftingtalstrasse 6
J. Stojsic: Clinical Center of Serbia, Pasterova 2
J. F. Deleuze: Université Paris-Saclay, 2 rue Gaston Crémieux, CP 5706
Z. Herceg: Section of Mechanisms of Carcinogenesis, 150 Cours Albert Thomas
A. Viari: Centre Léon Bérard, 28 Rue Laennec
P. Nuernberg: University of Cologne, Weyertal 115
G. Pelosi: University of Milan, and Inter-Hospital Pathology Division, IRCCS Multimedica, Via Gaudenzio Fantoli, 16/15
A. M. C. Dingemans: Maastricht University Medical Centre (MUMC), GROW School for Oncology and Developmental Biology, P.O. Box 5800
M. Milione: IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1
L. Roz: IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1
L. Brcic: Medical University of Graz, Neue Stiftingtalstrasse 6
M. Volante: University of Turin, Pathology Division, Via Santena 7
M. G. Papotti: University of Turin, Pathology Division, Via Santena 7
C. Caux: 28 Rue Laennec
J. Sandoval: Avenida Fernando Abril Martorell, Torre 106 A 7planta
H. Hernandez-Vargas: Université de Lyon, 28 Rue Laennec
E. Brambilla: Site Santé, Allée des Alpes
E. J. M. Speel: Maastricht University Medical Centre (MUMC), GROW School for Oncology and Developmental Biology, P.O. Box 5800
N. Girard: Institut Curie, 26 Rue d’Ulm
S. Lantuejoul: Centre Léon Bérard, 28 Rue Laennec
J. D. McKay: 150 Cours Albert Thomas
M. Foll: 150 Cours Albert Thomas
L. Fernandez-Cuesta: 150 Cours Albert Thomas

Nature Communications, 2019, vol. 10, issue 1, 1-21

Abstract: Abstract The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

Date: 2019
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DOI: 10.1038/s41467-019-11276-9

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