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


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.

SUBMITTER: Alcala N 

PROVIDER: S-EPMC6702229 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Alcala N N   Leblay N N   Gabriel A A G AAG   Gabriel A A G AAG   Mangiante L L   Hervas D D   Giffon T T   Sertier A S AS   Ferrari A A   Derks J J   Ghantous A A   Delhomme T M TM   Chabrier A A   Cuenin C C   Abedi-Ardekani B B   Boland A A   Olaso R R   Meyer V V   Altmuller J J   Le Calvez-Kelm F F   Durand G G   Voegele C C   Boyault S S   Moonen L L   Lemaitre N N   Lorimier P P   Toffart A C AC   Soltermann A A   Clement J H JH   Saenger J J   Field J K JK   Brevet M M   Blanc-Fournier C C   Galateau-Salle F F   Le Stang N N   Russell P A PA   Wright G G   Sozzi G G   Pastorino U U   Lacomme S S   Vignaud J M JM   Hofman V V   Hofman P P   Brustugun O T OT   Lund-Iversen M M   Thomas de Montpreville V V   Muscarella L A LA   Graziano P P   Popper H H   Stojsic J J   Deleuze J F JF   Herceg Z Z   Viari A A   Nuernberg P P   Pelosi G G   Dingemans A M C AMC   Milione M M   Roz L L   Brcic L L   Volante M M   Papotti M G MG   Caux C C   Sandoval J J   Hernandez-Vargas H H   Brambilla E E   Speel E J M EJM   Girard N N   Lantuejoul S S   McKay J D JD   Foll M M   Fernandez-Cuesta L L  

Nature communications 20190820 1


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 wit  ...[more]

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