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

Author

Listed:
  • 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
    Oslo University Hospital, Ullernchausseen 70)

  • 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
    University of Cologne, Joseph-Stelzmann-Straße 26)

  • 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
    European Reference Network (ERN-EURACAN), 28 rue Laennec)

  • S. Lantuejoul

    (Centre Léon Bérard, 28 Rue Laennec
    Cancer Genomic Platform, 28 Rue Laennec
    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)

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.

Suggested Citation

  • 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, 2019. "Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids," Nature Communications, Nature, vol. 10(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11276-9
    DOI: 10.1038/s41467-019-11276-9
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