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

@article{george2026integrative,
  title = {{Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors}},
  author = {Julie George and Vonn Walter and Martin Peifer and Ludmil B Alexandrov and Danila Seidel and Frauke Leenders and Lukas Maas and Christian Müller and Ilona Dahmen and Tiffany M Delhomme and Maude Ardin and Noemie Leblay and Graham Byrnes and Ruping Sun and Aurélien de Reynies and Anne Mcleer-Florin and Graziella Bosco and Florian Malchers and Roopika Menon and Janine Altmüller and Christian Becker and Peter Nürnberg and Viktor Achter and Ulrich Lang and Peter M Schneider and Magdalena Bogus and Matthew G Soloway and Matthew D Wilkerson and Yupeng Cun and James D Mckay and Denis Moro-Sibilot and Christian G Brambilla and Sylvie Lantuejoul and Nicolas Lemaitre and Alex Soltermann and Walter Weder and Verena Tischler and Odd Terje Brustugun and Marius Lund-Iversen and Åslaug Helland and Steinar Solberg and Sascha Ansén and Gavin Wright and Benjamin Solomon and Luca Roz and Ugo Pastorino and Iver Petersen and Joachim H Clement and Jörg Sänger and Jürgen Wolf and Martin Vingron and Thomas Zander and Sven Perner and William D Travis and Stefan A Haas and Magali Olivier and Matthieu Foll and Reinhard Büttner and David Neil Hayes and Elisabeth Brambilla},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-018-03099-x},
  url = {https://hal.science/hal-05842029v1},
  note = {CC BY},
}

TY  - JOUR
TI  - Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors
AU  - Julie George
AU  - Vonn Walter
AU  - Martin Peifer
AU  - Ludmil B Alexandrov
AU  - Danila Seidel
AU  - Frauke Leenders
AU  - Lukas Maas
AU  - Christian Müller
AU  - Ilona Dahmen
AU  - Tiffany M Delhomme
AU  - Maude Ardin
AU  - Noemie Leblay
AU  - Graham Byrnes
AU  - Ruping Sun
AU  - Aurélien de Reynies
AU  - Anne Mcleer-Florin
AU  - Graziella Bosco
AU  - Florian Malchers
AU  - Roopika Menon
AU  - Janine Altmüller
AU  - Christian Becker
AU  - Peter Nürnberg
AU  - Viktor Achter
AU  - Ulrich Lang
AU  - Peter M Schneider
AU  - Magdalena Bogus
AU  - Matthew G Soloway
AU  - Matthew D Wilkerson
AU  - Yupeng Cun
AU  - James D Mckay
AU  - Denis Moro-Sibilot
AU  - Christian G Brambilla
AU  - Sylvie Lantuejoul
AU  - Nicolas Lemaitre
AU  - Alex Soltermann
AU  - Walter Weder
AU  - Verena Tischler
AU  - Odd Terje Brustugun
AU  - Marius Lund-Iversen
AU  - Åslaug Helland
AU  - Steinar Solberg
AU  - Sascha Ansén
AU  - Gavin Wright
AU  - Benjamin Solomon
AU  - Luca Roz
AU  - Ugo Pastorino
AU  - Iver Petersen
AU  - Joachim H Clement
AU  - Jörg Sänger
AU  - Jürgen Wolf
AU  - Martin Vingron
AU  - Thomas Zander
AU  - Sven Perner
AU  - William D Travis
AU  - Stefan A Haas
AU  - Magali Olivier
AU  - Matthieu Foll
AU  - Reinhard Büttner
AU  - David Neil Hayes
AU  - Elisabeth Brambilla
PY  - 2026
DA  - 2026/10/28
JO  - Nature Communications
DO  - 10.1038/s41467-018-03099-x
UR  - https://hal.science/hal-05842029v1
AB  - 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.
SN  - 2041-1723
SN  - 2041-1723
ER  -