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Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer.

  • Anna K Karlsson
  • Hans Brunnström
  • Kajsa Ericson Lindquist
  • Karin Jirström
  • Mats Jönsson
  • Frida Rosengren
  • Christel Reuterswärd
  • Helena Cirenajwis
  • Åke Borg
  • Per Jönsson
  • Maria Planck
  • Göran B Jönsson
  • Johan Staaf
Publishing year: 2015
Language: English
Pages: 22028-22037
Publication/Series: Oncotarget
Volume: 6
Issue: 26
Document type: Journal article
Publisher: Impact Journals, LLC

Abstract english

Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes 3-9% of non-small cell lung cancer but is poorly characterized at the molecular level. Herein we analyzed 41 LC and 32 LCNEC (including 15 previously reported cases) tumors using massive parallel sequencing for mutations in 26 cancer-related genes and gene fusions in ALK, RET, and ROS1. LC patients were additionally subdivided into three immunohistochemistry groups based on positive expression of TTF-1/Napsin A (adenocarcinoma-like, n = 24; 59%), CK5/P40 (squamous-like, n = 5; 12%), or no marker expression (marker-negative, n = 12; 29%). Most common alterations were TP53 (83%), KRAS (22%), MET (12%) mutations in LCs, and TP53 (88%), STK11 (16%), and PTEN (13%) mutations in LCNECs. In general, LCs showed more oncogene mutations compared to LCNECs. Immunomarker stratification of LC revealed oncogene mutations in 63% of adenocarcinoma-like cases, but only in 17% of marker-negative cases. Moreover, marker-negative LCs were associated with inferior overall survival compared with adenocarcinoma-like tumors (p = 0.007). No ALK, RET or ROS1 fusions were detected in LCs or LCNECs. Together, our molecular analyses support that LC and LCNEC tumors follow different tumorigenic paths and that LC may be stratified into molecular subgroups with potential implications for diagnosis, prognostics, and therapy decisions.


  • Cancer and Oncology


  • CREATE Health
  • ISSN: 1949-2553
Åke Borg
Åke Borg
E-mail: ake [dot] borg [at] med [dot] lu [dot] se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2


Project manager

Familial Breast Cancer



Oncology and Pathology, MV

MV 404 C21C2