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., Durand, G., Voegele, C., Boyault, S., Moonen, L., Lemaitre, N., Lorimier, P., Toffart, A. C., Soltermann, A., Clement, J. H., Saenger, J., Field, J. K., Brevet, M., Blanc-Fournier, C., Galateau-Salle, F., Le Stang, N., Russell, P. A., Wright, G., Sozzi, G., Pastorino, U., Lacomme, S., Vignaud, J. M., Hofman, V, Hofman, P., Brustugun, O. T., Lund-Iversen, M., de Montpreville, V. Thomas, Muscarella, L. A., Graziano, P., Popper, H., Stojsic, J., Deleuze, J. F., Herceg, Z., Viari, A., Nuernberg, P., Pelosi, G., Dingemans, A. M. C., Milione, M., Roz, L., Brcic, L., Volante, M., Papotti, M. G., Caux, C., Sandoval, J., Hernandez-Vargas, H., Brambilla, E., Speel, E. J. M., Girard, N., Lantuejoul, S., McKay, J. D., Foll, M. and Fernandez-Cuesta, L. (2019). Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids. Nat. Commun., 10. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Alcala, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leblay, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gabriel, A. A. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mangiante, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hervas, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giffon, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sertier, A. S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferrari, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Derks, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ghantous, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delhomme, T. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chabrier, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cuenin, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abedi-Ardekani, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boland, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olaso, R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meyer, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmuller, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Le Calvez-Kelm, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Durand, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voegele, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boyault, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moonen, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lemaitre, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lorimier, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toffart, A. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soltermann, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clement, J. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saenger, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Field, J. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brevet, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanc-Fournier, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galateau-Salle, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Le Stang, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Russell, P. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wright, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sozzi, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pastorino, U.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lacomme, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vignaud, J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofman, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofman, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brustugun, O. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lund-Iversen, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Montpreville, V. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muscarella, L. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graziano, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popper, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stojsic, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deleuze, J. F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herceg, Z.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Viari, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pelosi, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dingemans, A. M. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milione, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roz, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brcic, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volante, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papotti, M. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caux, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sandoval, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hernandez-Vargas, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brambilla, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speel, E. J. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Girard, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lantuejoul, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McKay, J. D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foll, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Cuesta, L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-144098
DOI: 10.1038/s41467-019-11276-9
Journal or Publication Title: Nat. Commun.
Volume: 10
Date: 2019
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CELL LUNG-CANCER; NEUROENDOCRINE TUMORS; DENDRITIC CELLS; EXPRESSION; CLASSIFICATION; MUTATIONS; DISCOVERY; PATHWAY; HEALTH; IDENTIFICATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/14409

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