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

Karlsson, Anna K LU ; Brunnström, Hans LU ; Ericson Lindquist, Kajsa LU ; Jirström, Karin LU ; Jönsson, Mats LU ; Rosengren, Frida LU ; Reuterswärd, Christel LU ; Cirenajwis, Helena LU ; Borg, Åke LU and Jönsson, Per LU , et al. (2015) In Oncotarget 6(26). p.22028-22037
Abstract
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... (More)
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. (Less)
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Oncotarget
volume
6
issue
26
pages
22028 - 22037
publisher
Impact Journals, LLC
external identifiers
  • pmid:26124082
  • wos:000362954800037
  • scopus:84941248870
ISSN
1949-2553
project
CREATE Health
language
English
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yes
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d614e84d-0860-4b89-a9a2-6ec14114749e (old id 7751444)
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http://www.ncbi.nlm.nih.gov/pubmed/26124082?dopt=Abstract
date added to LUP
2015-08-01 20:40:36
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2017-10-22 04:11:57
@article{d614e84d-0860-4b89-a9a2-6ec14114749e,
  abstract     = {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.},
  author       = {Karlsson, Anna K and Brunnström, Hans and Ericson Lindquist, Kajsa and Jirström, Karin and Jönsson, Mats and Rosengren, Frida and Reuterswärd, Christel and Cirenajwis, Helena and Borg, Åke and Jönsson, Per and Planck, Maria and Jönsson, Göran B and Staaf, Johan},
  issn         = {1949-2553},
  language     = {eng},
  number       = {26},
  pages        = {22028--22037},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer.},
  volume       = {6},
  year         = {2015},
}