Background: Activating mutations in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) are predictive biomarkers for response to EGFR–tyrosine kinase inhibitor (TKI) therapy in lung adenocarcinoma (LUAD). Here, we characterized the clinicopathologic features associated with EGFR mutations via peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper) and evaluated the feasibility of targeted deep sequencing for detecting the mutations. Methods: We examined EGFR mutations in exons 18 through 21 for 2,088 LUADs from July 2017 to April 2020 using PANAMutyper. Of these, we performed targeted deep sequencing in 73 patients and evaluated EGFR-mutation status and TKI clinical response. Results: EGFR mutation was identified in 55.7% of LUADs by PANAMutyper, with mutation rates higher in females (69.3%) and never smokers (67.1%) and highest in the age range of 50 to 59 years (64.9%). For the 73 patients evaluated using both methods, next-generation sequencing (NGS) identified EGFR mutation–positive results in 14 of 61 patients (23.0%) who were EGFR-negative according to PANAMutyper testing. Of the 10 patients reportedly harboring a sensitizing mutation according to NGS, seven received TKI treatment, with all showing partial response or stable disease. In the 12 PANAMutyper-positive cases, NGS identified two additional mutations in exon 18, whereas a discordant negative result was observed in two cases. Conclusions Although PANAMutyper identified high frequencies of EGFR mutations, targeted deep sequencing revealed additional uncommon EGFR mutations. These findings suggested that appropriate use of NGS may benefit LUAD patients with otherwise negative screening test results.

Purpose: Pulmonary sarcomatoid carcinoma (PSC) is a rare aggressive subtype of non–small cell lung cancer (NSCLC) with limited therapeutic strategies. We attempted to elucidate the evolutionary trajectories of PSC using multiregional and longitudinal tumor samples. Materials and Methods: A total of 31 patients were enrolled in this study and 11 longitudinal samples were available from them. Using whole exome sequencing data, we analyzed the mutational signatures in both carcinomatous and sarcomatous areas in primary tumors of the 31 patients and longitudinal samples obtained from 11 patients. Furthermore, digital droplet polymerase chain reaction (ddPCR), and programmed death-ligand 1 (PD-L1) immunohistochemistry using the Ventana SP263 assay were performed. Results: TP53 was identified as the most frequently altered gene in the primary (74%) and metastatic (73%) samples. MET exon 14 skipping mutations, confirmed by ddPCR, and TP53 mutations were mutually exclusive; whereas, MET exon 14 skipping mutations frequently co-occurred with MDM2 amplification. Metastatic tumors showed dissimilar genetic profiles from either primary component. During metastasis, the signatures of APOBEC decreased in metastatic lesions compared with that in primary lesions. PSC showed higher MET and KEAP1 mutations and stronger PD-L1 protein expression compared with that recorded in other NSCLCs. Conclusion Decreased APOBEC signatures and subclonal diversity were detected during malignant progression in PSC. Frequent MET mutations and strong PD-L1 expression distinguished PSC from other NSCLCs. The aggressiveness and therapeutic difficulties of PSC were possibly attributable to profound intratumoral and intertumoral genetic diversity. Next-generation sequencing could suggest the appropriate treatment strategy for PSC.

BACKGROUND: Although the electronic cigarette (e-cigarette) market is growing rapidly, few studies have been conducted on e-cigarettes in South Korea. This study aims to analyze the general characteristics of Korean adult smokers with e-cigarette use.METHODS: This study used data from the 6th National Health and Nutrition Survey (NHANS). Multivariate logistic regression analysis was conducted to examine subjects' general characteristics and a questionnaire related to smoking cessation, stress perception, and depression. A frequency analysis of reasons for using e-cigarettes was conducted of 318 subjects of the 2015 NHANS who were smokers and used e-cigarettes.RESULTS: The study found that smokers with experience using e-cigarettes were younger and had a higher income level (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.03–2.05) than smokers without e-cigarette experience. Professional, management, and office worker groups were associated with e-cigarette use (OR, 1.40; 95% CI, 1.10–1.77). Willingness to quit smoking was also higher in subjects with experience using e-cigarettes (OR, 1.35; 95% CI, 1.09–1.68). The most common reason for smoking cessation in both groups was concern about their own and their family's health. About 50% of smokers with experience using e-cigarettes thought e-cigarettes would be more helpful for smoking cessation than regular cigarettes.CONCLUSION: Although the safety and rationale of using e-cigarettes as a smoking cessation aid are unproven, many smokers consider them a method of smoking cessation. It is necessary to provide correct information on e-cigarettes.
Adult ; Depression ; Electronic Cigarettes ; Humans ; Korea ; Logistic Models ; Methods ; Nutrition Surveys ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Products