{
  "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 / NOTCH low , type II LCNECs bear TP53 and RB1 alterations and differ from most SCLC tumors with reduced neuroendocrine markers, a pattern of ASCL1 low / DLL3 low / NOTCH high , 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.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 62,
  "authors": [
    {
      "name": "Julie George"
    },
    {
      "name": "Vonn Walter"
    },
    {
      "name": "Martin Peifer"
    },
    {
      "name": "Ludmil B Alexandrov"
    },
    {
      "name": "Danila Seidel"
    },
    {
      "name": "Frauke Leenders"
    },
    {
      "name": "Lukas Maas"
    },
    {
      "name": "Christian Müller"
    },
    {
      "name": "Ilona Dahmen"
    },
    {
      "name": "Tiffany M Delhomme"
    },
    {
      "name": "Maude Ardin"
    },
    {
      "name": "Noemie Leblay"
    },
    {
      "name": "Graham Byrnes"
    },
    {
      "name": "Ruping Sun"
    },
    {
      "name": "Aurélien de Reynies"
    },
    {
      "name": "Anne Mcleer-Florin"
    },
    {
      "name": "Graziella Bosco"
    },
    {
      "name": "Florian Malchers"
    },
    {
      "name": "Roopika Menon"
    },
    {
      "name": "Janine Altmüller"
    },
    {
      "name": "Christian Becker"
    },
    {
      "name": "Peter Nürnberg"
    },
    {
      "name": "Viktor Achter"
    },
    {
      "name": "Ulrich Lang"
    },
    {
      "name": "Peter M Schneider"
    },
    {
      "name": "Magdalena Bogus"
    },
    {
      "name": "Matthew G Soloway"
    },
    {
      "name": "Matthew D Wilkerson"
    },
    {
      "name": "Yupeng Cun"
    },
    {
      "name": "James D Mckay"
    },
    {
      "name": "Denis Moro-Sibilot"
    },
    {
      "name": "Christian G Brambilla"
    },
    {
      "name": "Sylvie Lantuejoul"
    },
    {
      "name": "Nicolas Lemaitre"
    },
    {
      "name": "Alex Soltermann"
    },
    {
      "name": "Walter Weder"
    },
    {
      "name": "Verena Tischler"
    },
    {
      "name": "Odd Terje Brustugun"
    },
    {
      "name": "Marius Lund-Iversen"
    },
    {
      "name": "Åslaug Helland"
    },
    {
      "name": "Steinar Solberg"
    },
    {
      "name": "Sascha Ansén"
    },
    {
      "name": "Gavin Wright"
    },
    {
      "name": "Benjamin Solomon"
    },
    {
      "name": "Luca Roz"
    },
    {
      "name": "Ugo Pastorino"
    },
    {
      "name": "Iver Petersen"
    },
    {
      "name": "Joachim H Clement"
    },
    {
      "name": "Jörg Sänger"
    },
    {
      "name": "Jürgen Wolf"
    },
    {
      "name": "Martin Vingron"
    },
    {
      "name": "Thomas Zander"
    },
    {
      "name": "Sven Perner"
    },
    {
      "name": "William D Travis"
    },
    {
      "name": "Stefan A Haas"
    },
    {
      "name": "Magali Olivier"
    },
    {
      "name": "Matthieu Foll"
    },
    {
      "name": "Reinhard Büttner"
    },
    {
      "name": "David Neil Hayes"
    },
    {
      "name": "Elisabeth Brambilla"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4678g4k19zknz.bib",
  "cited_by": 379,
  "doi": "10.1038/s41467-018-03099-x",
  "fulltext_url": null,
  "id": "4678g4k19zknz",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://hal.science/hal-05842029v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.can"
    ],
    [
      "openalex",
      "2730|Lung Cancer Research Studies"
    ]
  ],
  "openalex": "W2792828274",
  "pdf_url": "https://www.nature.com/articles/s41467-018-03099-x.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/4678g4k19zknz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "hal-05842029",
      "source": "hal",
      "url": "https://hal.science/hal-05842029v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "hal:0.sdv",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.can",
      "subfield": "oncology"
    }
  ],
  "title": "Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors",
  "title_text": "Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/4678g4k19zknz",
  "venue": "Nature Communications",
  "versions": []
}