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

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. Boland, R. Olaso, V. Meyer, J. Altmuller, F. Le Calvez-Kelm, G. DurandC. Voegele, S. Boyault, L. Moonen, N. Lemaitre, P. Lorimier, A. C. Toffart, A. Soltermann, J. H. Clement, J. Saenger, J. K. Field, M. Brevet, C. Blanc-Fournier, F. Galateau-Salle, N. Le Stang, P. A. Russell, G. Wright, G. Sozzi, U. Pastorino, S. Lacomme, J. M. Vignaud, V. Hofman, P. Hofman, O. T. Brustugun, M. Lund-Iversen, V. Thomas de Montpreville, L. A. Muscarella, P. Graziano, H. Popper, J. Stojsic, J. F. Deleuze, Z. Herceg, A. Viari, P. Nuernberg, G. Pelosi, A. M.C. Dingemans, M. Milione, L. Roz, L. Brcic, M. Volante, M. G. Papotti, C. Caux, J. Sandoval, H. Hernandez-Vargas, E. Brambilla, E. J.M. Speel, N. Girard, S. Lantuejoul, J. D. McKay, M. Foll, L. Fernandez-Cuesta

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number3407
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

    Fingerprint

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Alcala, N., Leblay, N., Gabriel, A. A. G., Mangiante, L., Hervas, D., Giffon, T., Sertier, A. S., Ferrari, A., Derks, J., Ghantous, A., Delhomme, T. M., Chabrier, A., Cuenin, C., Abedi-Ardekani, B., Boland, A., Olaso, R., Meyer, V., Altmuller, J., Le Calvez-Kelm, F., ... Fernandez-Cuesta, L. (2019). Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids. Nature Communications, 10(1), [3407]. https://doi.org/10.1038/s41467-019-11276-9