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

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11276-9

2041-1723

Nicolas Alcala, Noémie Leblay, Alice‐Agnes Gabriel, Lise Mangiante, David Hervás, Théo Giffon, Anne-Sophie Sertier, Anthony Ferrari, Jules L. Derks, A. Ghantous, Tiffany M. Delhomme, Amélie Chabrier, Cyrille Cuenin, Behnoush Abedi‐Ardekani, Anne Boland, Robert Olaso, Vincent Meyer, Janine Altmüller, Florence Le Calvez‐Kelm, Geoffroy Durand, Catherine Voegele, Sandrine Boyault, Laura Moonen, Nicole Lemaître, P. Lorimier, Anne‐Claire Toffart, Alex Soltermann, Joachim H. Clement, Joerg Saenger, John K. Field, Marie Brevet, Cécile Blanc‐Fournier, Françoise Galateau-Sallé, Nolwenn Le Stang, Prudence A. Russell, Gavin Wright, Gabriella Sozzi, Ugo Pastorino, Stéphanie Lacomme, J Vignaud, Véronique Hofman, Paul Hofman, Odd Terje Brustugun, Marius Lund‐Iversen, Vincent de Montpréville, Lucia Anna Muscarella, Paolo Graziano, Helmut Popper, Jelena Stojšić, Jean‐François Deleuze, Zdenko Herceg, Alain Viari, Peter Nüernberg, Giuseppe Pelosi, Anne‐Marie C. Dingemans, Massimo Milione, Luca Roz, Luka Brčić, Marco Volante, Mauro Papotti, Christophe Caux, Juan Sandoval, Héctor Hernández‐Vargas, Élisabeth Brambilla, E.J.M. Speel, Nicolas Girard, Sylvie Lantuéjoul, James McKay, Matthieu Foll, Lynnette Fernández-Cuesta,

Neuroblastoma Research and Treatments

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.