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]
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]
Nicolas Alcala
- Fonction : Auteur
- PersonId : 778162
- ORCID : 0000-0002-5961-5064
Lise Mangiante
- Fonction : Auteur
- PersonId : 797840
- ORCID : 0000-0001-8309-0950
Davis Hervás
- Fonction : Auteur
- PersonId : 885358
Amélie Chabrier
- Fonction : Auteur
- PersonId : 743312
- IdHAL : amelie-chabrier
Anne Boland
- Fonction : Auteur
- PersonId : 757786
- ORCID : 0000-0001-8789-5676
Robert Olaso
- Fonction : Auteur
- PersonId : 774936
- ORCID : 0000-0001-7631-9657
Catherine Voegele
- Fonction : Auteur
- PersonId : 771118
- IdRef : 193031205
Sandrine Boyault
- Fonction : Auteur
- PersonId : 757688
- IdRef : 075706466
Paul Hofman
- Fonction : Auteur
- PersonId : 760269
- ORCID : 0000-0003-0431-9353
- IdRef : 061092630
Vincent Thomas de Montpreville
- Fonction : Auteur
- PersonId : 797841
- ORCID : 0000-0001-7490-4000
Alain Viari
- Fonction : Auteur
- PersonId : 18170
- IdHAL : alain-viari
- ORCID : 0000-0002-1329-7777
- IdRef : 081478151
Christophe Caux
- Fonction : Auteur
- PersonId : 928809
- IdHAL : christophe-caux
- ORCID : 0000-0003-2438-833X
- IdRef : 08417854X
Hector Hernandez-Vargas
- Fonction : Auteur
- PersonId : 768730
- IdHAL : hernandez-vargas-h
- ORCID : 0000-0001-6045-2103
- IdRef : 175457689
Lynnette Fernandez-Cuesta
- Fonction : Auteur
- PersonId : 797842
- ORCID : 0000-0002-0724-6703
- IdRef : 233420819
Résumé
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.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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