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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; [...]

Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors

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  • Medientyp: E-Artikel
  • Titel: Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors
  • Beteiligte: 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; [...]
  • Erschienen: Springer Science and Business Media LLC, 2018
  • Erschienen in: Nature Communications
  • Sprache: Englisch
  • DOI: 10.1038/s41467-018-03099-x
  • ISSN: 2041-1723
  • Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 (<jats:italic>n</jats:italic> = 60) and transcriptomic (<jats:italic>n</jats:italic> = 69) analysis of 75 LCNECs and identify two molecular subgroups: “type I LCNECs” with bi-allelic <jats:italic>TP53</jats:italic> and <jats:italic>STK11</jats:italic>/<jats:italic>KEAP1</jats:italic> alterations (37%), and “type II LCNECs” enriched for bi-allelic inactivation of <jats:italic>TP53</jats:italic> and <jats:italic>RB1</jats:italic> (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 <jats:italic>ASCL1</jats:italic><jats:sup>high</jats:sup>/<jats:italic>DLL3</jats:italic><jats:sup>high</jats:sup>/<jats:italic>NOTCH</jats:italic><jats:sup>low</jats:sup>, type II LCNECs bear <jats:italic>TP53</jats:italic> and <jats:italic>RB1</jats:italic> alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of <jats:italic>ASCL1</jats:italic><jats:sup>low</jats:sup>/<jats:italic>DLL3</jats:italic><jats:sup>low</jats:sup>/<jats:italic>NOTCH</jats:italic><jats:sup>high</jats:sup>, 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.</jats:p>
  • Zugangsstatus: Freier Zugang