J Korean Med Sci.  2017 Mar;32(3):415-420. 10.3346/jkms.2017.32.3.415.

Analysis of Fifty Hotspot Mutations of Lung Squamous Cell Carcinoma in Never-smokers

• Lee HY
• Lee SH
• Won JK
• Lee DS
• Kwon NJ
• Choi SM
• Lee J
• Lee CH
• Lee SM
• Yim JJ
• Yoo CG
• Kim YW
• Han SK
• Park YS

• KMID: 2366636
• DOI: http://doi.org/10.3346/jkms.2017.32.3.415

Abstract

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.

Keyword

Lung Cancer; Squamous Cell Carcinoma; Never-Smoker; Mutation; TP53; RAS; STK11

MeSH Terms

Carcinoma, Squamous Cell*
Epithelial Cells*
Female
Genome
Humans
Incidence
Lung Neoplasms
Lung*
Medical Records
Retrospective Studies
Risk Factors
Seoul
Smoke
Smoking
Smoke

Figure

• 

  Fig. 1 Mutational profiles of lung SCC in never-smokers and ever-smokers. Heatmap representation of individual mutations present in 26 lung SCC samples (12 from never-smokers and 14 from ever-smokers). Percentages refer to the proportion of samples that carried at least 1 mutation in the listed gene (right). RAS is a conglomerated representation of HRAS and KRAS. SCC = squamous cell carcinoma, SNP = single-nucleotide polymorphism.

• 

  Fig. 2 OS of patients with lung SCC based on smoking history. (A) OS of all lung SCC patients (n = 379). (B) OS of patients matched by age and stage at a 1:3 ratio (n = 76). The P value was calculated using the log-rank test. OS = overall survival, SCC = squamous cell carcinoma.

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