George, Julie, Walter, Vonn ORCID: 0000-0001-6114-6714, Peifer, Martin, Alexandrov, Ludmil B., Seidel, Danila ORCID: 0000-0003-4388-3117, Leenders, Frauke, Maas, Lukas, Mueller, Christian, Dahmen, Ilona, Delhomme, Tiffany M. ORCID: 0000-0003-0265-4246, Ardin, Maude, Leblay, Noemie, Byrnes, Graham ORCID: 0000-0003-3893-7539, Sun, Ruping, De Reynies, Aurelien, McLeer-Florin, Anne, Bosco, Graziella, Malchers, Florian, Menon, Roopika, Altmuller, Janine, Becker, Christian, Nurnberg, Peter, Achter, Viktor, Lang, Ulrich, Schneider, Peter M. ORCID: 0000-0003-0744-2349, Bogus, Magdalena, Soloway, Matthew G., Wilkerson, Matthew D., Cun, Yupeng ORCID: 0000-0002-4241-8099, McKay, James D., Moro-Sibilot, Denis, Brambilla, Christian G., Lantuejoul, Sylvie, Lemaitre, Nicolas, Soltermann, Alex, Weder, Walter, Tischler, Verena ORCID: 0000-0002-6673-8329, Brustugun, Odd Terje, Lund-Iversen, Marius, Helland, Aslaug ORCID: 0000-0002-5520-0275, Solberg, Steinar, Ansen, Sascha, Wright, Gavin, Solomon, Benjamin, Roz, Luca ORCID: 0000-0001-5817-7149, Pastorino, Ugo, Petersen, Iver, Clement, Joachim H. ORCID: 0000-0002-6601-2456, Saenger, Jorg, Wolf, Jurgen, Vingron, Martin, Zander, Thomas, Perner, Sven, Travis, William D., Haas, Stefan A., Olivier, Magali, Foll, Matthieu ORCID: 0000-0001-9006-8436, Buettner, Reinhard, Hayes, David Neil, Brambilla, Elisabeth, Fernandez-Cuesta, Lynnette ORCID: 0000-0002-0724-6703 and Thomas, Roman K. (2018). Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nat. Commun., 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

Full text not available from this repository.

Abstract

Pulmonary large-cell neuroendocrine carcinomas (LCNECs) have similarities with other lung cancers, but their precise relationship has remained unclear. Here we perform a comprehensive genomic (n = 60) and transcriptomic (n = 69) analysis of 75 LCNECs and identify two molecular subgroups: type I LCNECs with bi-allelic TP53 and STK11/KEAP1 alterations (37%), and type II LCNECs enriched for bi-allelic inactivation of TP53 and RB1 (42%). Despite sharing genomic alterations with adenocarcinomas and squamous cell carcinomas, no transcriptional relationship was found; instead LCNECs form distinct transcriptional subgroups with closest similarity to SCLC. While type I LCNECs and SCLCs exhibit a neuroendocrine profile with ASCL1(high)/DLL3(high)/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1l(ow)/DLL3(low)/NOTCHhigh, and an upregulation of immune-related pathways. In conclusion, LCNECs comprise two molecularly defined subgroups, and distinguishing them from SCLC may allow stratified targeted treatment of high-grade neuroendocrine lung tumors.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
George, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walter, VonnUNSPECIFIEDorcid.org/0000-0001-6114-6714UNSPECIFIED
Peifer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Alexandrov, Ludmil B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seidel, DanilaUNSPECIFIEDorcid.org/0000-0003-4388-3117UNSPECIFIED
Leenders, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maas, LukasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dahmen, IlonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delhomme, Tiffany M.UNSPECIFIEDorcid.org/0000-0003-0265-4246UNSPECIFIED
Ardin, MaudeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leblay, NoemieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Byrnes, GrahamUNSPECIFIEDorcid.org/0000-0003-3893-7539UNSPECIFIED
Sun, RupingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Reynies, AurelienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McLeer-Florin, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bosco, GraziellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malchers, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menon, RoopikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmuller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nurnberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Achter, ViktorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, Peter M.UNSPECIFIEDorcid.org/0000-0003-0744-2349UNSPECIFIED
Bogus, MagdalenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soloway, Matthew G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilkerson, Matthew D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cun, YupengUNSPECIFIEDorcid.org/0000-0002-4241-8099UNSPECIFIED
McKay, James D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moro-Sibilot, DenisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brambilla, Christian G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lantuejoul, SylvieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lemaitre, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Soltermann, AlexUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weder, WalterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tischler, VerenaUNSPECIFIEDorcid.org/0000-0002-6673-8329UNSPECIFIED
Brustugun, Odd TerjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lund-Iversen, MariusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Helland, AslaugUNSPECIFIEDorcid.org/0000-0002-5520-0275UNSPECIFIED
Solberg, SteinarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ansen, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wright, GavinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solomon, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roz, LucaUNSPECIFIEDorcid.org/0000-0001-5817-7149UNSPECIFIED
Pastorino, UgoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petersen, IverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Clement, Joachim H.UNSPECIFIEDorcid.org/0000-0002-6601-2456UNSPECIFIED
Saenger, JorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vingron, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perner, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Travis, William D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haas, Stefan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olivier, MagaliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Foll, MatthieuUNSPECIFIEDorcid.org/0000-0001-9006-8436UNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hayes, David NeilUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brambilla, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fernandez-Cuesta, LynnetteUNSPECIFIEDorcid.org/0000-0002-0724-6703UNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-192760
DOI: 10.1038/s41467-018-03099-x
Journal or Publication Title: Nat. Commun.
Volume: 9
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LARGE GENE LISTS; MUTATIONAL PROCESSES; NONSMALL CELL; CANCER; ADENOCARCINOMA; EXPRESSION; CLASSIFICATION; HETEROGENEITY; MICROARRAYS; SIGNATURESMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19276

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item