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 Popper 24 Jelena Stojsic 25 Jean-Francois Deleuze 5 Zdenko Herceg 1 Alain Viari 26 Peter Nuernberg 6, 7 Giuseppe Pelosi 27 Anne-Marie 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
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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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, Nature Publishing Group, 2019, 10 (1), pp.1-21. ⟨10.1038/s41467-019-11276-9⟩. ⟨hal-02339242⟩

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