Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers.
Smoking is the major risk factor for lung squamous cell carcinoma (SCC), although a small number of lung SCCs occurs in never-smokers. The purpose of this study was to compare 50 hotspot mutations of lung SCCs between never-smokers and smokers. We retrospectively reviewed the medical records of patients newly diagnosed with lung SCC between January 1, 2011 and December 31, 2013 in the Seoul National University Hospital. Formalin-fixed, paraffin-embedded tumor samples were used for analysis of hotspot mutations. Fifty cancer-related genes in never-smokers were compared to those in ever-smokers. Of 379 lung SCC patients, 19 (5.0%) were never-smokers. The median age of these 19 patients was 67 years (interquartile range 57-73 years), and 10 of these patients were women (52.5%). The incidence rates of stage I, II, III, and IV disease in this group were 26.4%, 5.3%, 31.6%, and 36.8%, respectively, and sequencing was performed successfully in 14 cases. In the 26 lung SCC tumor samples (12 from never-smokers and 14 from ever-smokers) sequenced using personal genome machine, the most common mutations were in TP53 (75.0%), RAS (66.7%), and STK11 (33.3%), but mutations were also found in EGFR, KIT, and PTEN. The distribution of hotspot mutations in never-smokers was similar to that in ever-smokers. There was no significant difference in overall survival between the 2 groups. The 50 hotspot mutations of lung SCC in never-smokers were similar to those of ever-smokers.
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Ha Youn
http://orcid.org/0000-0002-7664-3120
HY
Lee
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Se Hoon
http://orcid.org/0000-0002-9219-3350
SH
Lee
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Jae Kyung
http://orcid.org/0000-0003-1459-8093
JK
Won
Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, Korea.
Dong Soo
http://orcid.org/0000-0001-9013-4835
DS
Lee
Macrogen Inc., Seoul, Korea.
Nak Jung
http://orcid.org/0000-0003-0874-4146
NJ
Kwon
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Sun Mi
http://orcid.org/0000-0002-0742-6085
SM
Choi
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jinwoo
http://orcid.org/0000-0003-0958-106X
J
Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Chang Hoon
http://orcid.org/0000-0001-9960-1524
CH
Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Sang Min
http://orcid.org/0000-0002-1388-9318
SM
Lee
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jae Joon
http://orcid.org/0000-0002-9605-0074
JJ
Yim
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Chul Gyu
http://orcid.org/0000-0003-1321-7834
CG
Yoo
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Young Whan
http://orcid.org/0000-0002-2768-2422
YW
Kim
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Sung Koo
http://orcid.org/0000-0003-0876-9781
SK
Han
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea. mdyspark@gmail.com.
Young Sik
http://orcid.org/0000-0003-0235-6943
YS
Park
D000091162:AMP-Activated Protein Kinase Kinases; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012189:Retrospective Studies; D012907:Smoking; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D018631:ras Proteins
Lung Cancer; Mutation; Never-Smoker; RAS; STK11; Squamous Cell Carcinoma; TP53