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Journal Articles Nature Communications Year : 2019

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

Nicolas Alcala (1) , Noémie Leblay (1) , Aurélie Gabriel (1) , Lise Mangiante (1) , Davis Hervás (2) , T. Giffon (1) , Anne-Sophie Sertier (3) , Anthony Ferrari (3) , Jules Derks (4) , Akram Ghantous (1) , Tiffany Delhomme (1) , Amélie Chabrier (1) , Cyrille Cuenin (1) , Behnoush Abedi-Ardekani (1) , Anne Boland (5) , Robert Olaso (5) , Vincent Meyer (5) , Janine Altmuller (6, 7) , Florence Le Calvez-Kelm (1) , Geoffroy Durand (1) , Catherine Voegele (1) , Sandrine Boyault (3) , Laura Moonen (4, 8) , Nicolas Lemaître (9) , Philippe Lorimier (9) , Anne-Claire Toffart (10) , Alex Soltermann (11) , Joachim Clement (12) , Jörg Saenger (13) , John Field (14) , Marie Brevet (15) , Cécile Blanc-Fournier (16) , Françoise Galateau-Sallé (15) , Nolwenn Le Stang (15) , Prue Russell (17) , Gavin Wright (17) , Gabriella Sozzi (18) , Ugo Pastorino (18) , Stéphanie Lacomme (19) , Jean Vignaud (19) , Véronique Hofman (20) , Paul Hofman (20) , Odd Terje Brustugun (21) , Marius Lund-Iversen (21) , Vincent Thomas de Montpreville (22) , Lucia Anna Muscarella (23) , Paolo Graziano (23) , Helmut H. Popper (24) , Jelena Stojsic (25) , Jean-Francois Deleuze (5) , Zdenko Herceg (1) , Alain Viari (26) , Peter Nuernberg (6, 7) , Giuseppe Pelosi (27) , Anne-Marie C. Dingemans (4) , Massimo Milione (18) , Luca Roz (18) , Luka Brcic (24) , Marco Volante (28) , Mauro Papotti (28) , Christophe Caux (29) , J. Sandoval (2) , Hector Hernandez-Vargas (29) , Elizabeth Brambilla (9) , E. Speel (4) , Nicolas Girard (29) , Sylvie Lantuéjoul (30) , James Mckay (1) , M. Foll (1) , Lynnette Fernandez-Cuesta (1)
1 CIRC - Centre international de Recherche sur le Cancer
2 Hospital Universitari i Politècnic La Fe = University and Polytechnic Hospital La Fe
3 Fondation Synergie Lyon Cancer [Lyon]
4 MUMC - Maastricht University Medical Centre
5 JACOB - Institut de Biologie François JACOB
6 CCG - Cologne Center for Genomics [Cologne]
7 CMMC - Centre for Molecular Medicine Cologne [Cologne]
8 GROW - School for Oncology and Developmental Biology [Maastricht]
9 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
10 Service de pneumologie [Grenoble]
11 Institute of Pathology and Molecular Pathology [Zurich]
12 Department Hematology and Medical Oncology [Jena]
13 Central Clinic Bad Berka
14 Department of Molecular and Clinical Cancer Medicine [Liverpool]
15 UCBL - Université Claude Bernard Lyon 1
16 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
17 University of Melbourne
18 IRCCS Istituto Nazionale dei Tumori [Milano]
19 NGERE - Nutrition-Génétique et Exposition aux Risques Environnementaux
20 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
21 Oslo University Hospital [Oslo]
22 CCML - Centre Chirurgical Marie Lannelongue
23 IRCCS - Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo]
24 University Hospital Graz
25 KCS - Clinical Center of Serbia
26 ERABLE - Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale
27 UNIMI - Università degli Studi di Milano = University of Milan
28 UNITO - Università degli studi di Torino = University of Turin
29 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
30 Centre Léon Bérard [Lyon]
Anne Boland
Robert Olaso
Sandrine Boyault
  • Function : Author
  • PersonId : 757688
  • IdRef : 075706466
Anne-Claire Toffart
  • Function : Author
  • PersonId : 855543
Marie Brevet
  • Function : Author
  • PersonId : 1202971

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 car-cinoids, 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.
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Dates and versions

hal-02339242 , version 1 (30-10-2019)

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Nicolas Alcala, Noémie Leblay, Aurélie Gabriel, Lise Mangiante, Davis Hervás, et al.. Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids. Nature Communications, 2019, 10 (1), pp.1-21. ⟨10.1038/s41467-019-11276-9⟩. ⟨hal-02339242⟩
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