Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors
dc.date.accessioned | 2019-01-23T15:45:02Z | |
dc.date.available | 2019-01-23T15:45:02Z | |
dc.date.created | 2018-07-24T12:23:42Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | George, Julie Walter, Vonn Peifer, Martin Alexandrov, Ludmil B. Seidel, Danila Leenders, Frauke Maas, Lukas Müller, Christian Dahmen, Ilona Delhomme, Tiffany M. Ardin, Maude Leblay, Noemie Byrnes, Graham Sun, Ruping De Reynies, Aurélien McLeer-Florin, Anne Bosco, Graziella Malchers, Florian Menon, Roopika Altmüller, Janine Becker, Christian Nürnberg, Peter Achter, Viktor Lang, Ulrich Schneider, Peter M. Bogus, Magdalena Soloway, Matthew G. Wilkerson, Matthew D. Cun, Yupeng McKay, James D. Moro-Sibilot, Denis Brambilla, Christian G. Lantuejoul, Sylvie Lemaitre, Nicolas Soltermann, Alex Weder, Walter Tischler, Verena Brustugun, Odd Terje Lund-Iversen, Marius Helland, Åslaug Solberg, Steinar Ansén, Sascha Wright, Gavin Solomon, Benjamin Roz, Luca Pastorino, Ugo Petersen, Iver Clement, Joachim H. Sänger, Jörg Wolf, Jürgen Vingron, Martin Zander, Thomas Perner, Sven Travis, William D. Haas, Stefan A. Olivier, Magali Foll, Matthieu Büttner, Reinhard Hayes, David Neil Brambilla, Elisabeth Fernandez-Cuesta, Lynnette Thomas, Roman K. . Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors. Nature Communications. 2018, 9:1048, 1-13 | |
dc.identifier.uri | http://hdl.handle.net/10852/66301 | |
dc.description.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 ASCL1high/DLL3high/NOTCHlow, type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1low/DLL3low/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. | en_US |
dc.language | EN | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors | en_US |
dc.title.alternative | ENEngelskEnglishIntegrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors | |
dc.type | Journal article | en_US |
dc.creator.author | George, Julie | |
dc.creator.author | Walter, Vonn | |
dc.creator.author | Peifer, Martin | |
dc.creator.author | Alexandrov, Ludmil B. | |
dc.creator.author | Seidel, Danila | |
dc.creator.author | Leenders, Frauke | |
dc.creator.author | Maas, Lukas | |
dc.creator.author | Müller, Christian | |
dc.creator.author | Dahmen, Ilona | |
dc.creator.author | Delhomme, Tiffany M. | |
dc.creator.author | Ardin, Maude | |
dc.creator.author | Leblay, Noemie | |
dc.creator.author | Byrnes, Graham | |
dc.creator.author | Sun, Ruping | |
dc.creator.author | De Reynies, Aurélien | |
dc.creator.author | McLeer-Florin, Anne | |
dc.creator.author | Bosco, Graziella | |
dc.creator.author | Malchers, Florian | |
dc.creator.author | Menon, Roopika | |
dc.creator.author | Altmüller, Janine | |
dc.creator.author | Becker, Christian | |
dc.creator.author | Nürnberg, Peter | |
dc.creator.author | Achter, Viktor | |
dc.creator.author | Lang, Ulrich | |
dc.creator.author | Schneider, Peter M. | |
dc.creator.author | Bogus, Magdalena | |
dc.creator.author | Soloway, Matthew G. | |
dc.creator.author | Wilkerson, Matthew D. | |
dc.creator.author | Cun, Yupeng | |
dc.creator.author | McKay, James D. | |
dc.creator.author | Moro-Sibilot, Denis | |
dc.creator.author | Brambilla, Christian G. | |
dc.creator.author | Lantuejoul, Sylvie | |
dc.creator.author | Lemaitre, Nicolas | |
dc.creator.author | Soltermann, Alex | |
dc.creator.author | Weder, Walter | |
dc.creator.author | Tischler, Verena | |
dc.creator.author | Brustugun, Odd Terje | |
dc.creator.author | Lund-Iversen, Marius | |
dc.creator.author | Helland, Åslaug | |
dc.creator.author | Solberg, Steinar | |
dc.creator.author | Ansén, Sascha | |
dc.creator.author | Wright, Gavin | |
dc.creator.author | Solomon, Benjamin | |
dc.creator.author | Roz, Luca | |
dc.creator.author | Pastorino, Ugo | |
dc.creator.author | Petersen, Iver | |
dc.creator.author | Clement, Joachim H. | |
dc.creator.author | Sänger, Jörg | |
dc.creator.author | Wolf, Jürgen | |
dc.creator.author | Vingron, Martin | |
dc.creator.author | Zander, Thomas | |
dc.creator.author | Perner, Sven | |
dc.creator.author | Travis, William D. | |
dc.creator.author | Haas, Stefan A. | |
dc.creator.author | Olivier, Magali | |
dc.creator.author | Foll, Matthieu | |
dc.creator.author | Büttner, Reinhard | |
dc.creator.author | Hayes, David Neil | |
dc.creator.author | Brambilla, Elisabeth | |
dc.creator.author | Fernandez-Cuesta, Lynnette | |
dc.creator.author | Thomas, Roman K. | |
cristin.unitcode | 185,53,49,10 | |
cristin.unitname | Avdeling for kreftbehandling | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 1598474 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature Communications&rft.volume=9:1048&rft.spage=1&rft.date=2018 | |
dc.identifier.jtitle | Nature Communications | |
dc.identifier.volume | 9:1048 | |
dc.identifier.startpage | 1 | |
dc.identifier.endpage | 13 | |
dc.identifier.doi | http://dx.doi.org/10.1038/s41467-018-03099-x | |
dc.identifier.urn | URN:NBN:no-69511 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 2041-1723 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/66301/1/Integrative%2Bgenomic%2Bprofiling%2Bof%2Blarge-cell%2Bneuroendocrine%2Bcarcinomas%2Breveals%2Bdistinct%2Bsubtypes%2Bof%2Bhigh-grade%2Bneuroendocrine%2Blung%2Btumors.pdf | |
dc.type.version | PublishedVersion |
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