16P - Comprehensive Analysis of Driver Mutations in Chinese Squamous Cell Lung Carcinomas By Targeted Next-Generation Sequencing

Abstract

Aim: Identification of driver mutations has led to the dramatic improvement in personalized therapy for lung adenocarcinoma. However, few targeted therapeutics are approved for treatment of squamous cell lung carcinoma (SqCLC). The identification of druggable molecular targets in SqCLC has been becoming a top research priority. We therefore analyzed the driver mutation profiles in a large cohort of Chinese SqCLCs to identify potential therapeutic targets.Methods: One hundred and seventy-two formalin-fixed paraffin-embedded samples of SqCLC were collected. We detected approximately 2,800 COSMIC mutations from 50 oncogenes and tumor suppressor genes on 159 samples by using Ion Torrent semiconductor-based next-generation sequencing. In addition, we conducted FISH for FGFR1 amplification and IHC for loss of PTEN expression on 172 samples.Results: Somatic mutations were detected in 73.6% (117/159) of patients. The most commonly mutated gene detected in this study was TP53 (89 cases, 56.0%), followed by CDKN2A (14 cases, 8.8%), PI3KCA (14 cases, 8.8%), KRAS (7 cases, 4.4%), and EGFR (5 cases, 3.1%). The incidences of FGFR1 amplification and loss of PTEN expression in this cohort of patients were 16.9 % (29/172) and 43.6% (75/172), respectively. The frequency of EGFR mutation was significantly higher in female and never smokers, while TP53 mutations were significantly more common in men and smokers. The incidence of FGFR1 amplification in current smokers was significantly higher than that in former smokers and never smokers (Ptrend = 0.025). Loss of PTEN expression was more frequent in elders (P = 0.047), male gender (P = 0.033), patients with early stage (P = 0.042) and positive pleural invasion (P = 0.030). No significant association was observed between the molecular abnormalities and overall survival.Conclusions: Somatic mutations were detected in nearly three-fourth (73.6%) of Chinese SqCLC patients. FGFR1 amplification and loss of PTEN expression are also frequent alterations in SqCLC. Comprehensive analysis of driver mutations in our study could facilitate the development of targetd therapies and optimize the therapeutic strategies for patients with SqCLC.Disclosure: All authors have declared no conflicts of interest. Aim: Identification of driver mutations has led to the dramatic improvement in personalized therapy for lung adenocarcinoma. However, few targeted therapeutics are approved for treatment of squamous cell lung carcinoma (SqCLC). The identification of druggable molecular targets in SqCLC has been becoming a top research priority. We therefore analyzed the driver mutation profiles in a large cohort of Chinese SqCLCs to identify potential therapeutic targets. Methods: One hundred and seventy-two formalin-fixed paraffin-embedded samples of SqCLC were collected. We detected approximately 2,800 COSMIC mutations from 50 oncogenes and tumor suppressor genes on 159 samples by using Ion Torrent semiconductor-based next-generation sequencing. In addition, we conducted FISH for FGFR1 amplification and IHC for loss of PTEN expression on 172 samples. Results: Somatic mutations were detected in 73.6% (117/159) of patients. The most commonly mutated gene detected in this study was TP53 (89 cases, 56.0%), followed by CDKN2A (14 cases, 8.8%), PI3KCA (14 cases, 8.8%), KRAS (7 cases, 4.4%), and EGFR (5 cases, 3.1%). The incidences of FGFR1 amplification and loss of PTEN expression in this cohort of patients were 16.9 % (29/172) and 43.6% (75/172), respectively. The frequency of EGFR mutation was significantly higher in female and never smokers, while TP53 mutations were significantly more common in men and smokers. The incidence of FGFR1 amplification in current smokers was significantly higher than that in former smokers and never smokers (Ptrend = 0.025). Loss of PTEN expression was more frequent in elders (P = 0.047), male gender (P = 0.033), patients with early stage (P = 0.042) and positive pleural invasion (P = 0.030). No significant association was observed between the molecular abnormalities and overall survival. Conclusions: Somatic mutations were detected in nearly three-fourth (73.6%) of Chinese SqCLC patients. FGFR1 amplification and loss of PTEN expression are also frequent alterations in SqCLC. Comprehensive analysis of driver mutations in our study could facilitate the development of targetd therapies and optimize the therapeutic strategies for patients with SqCLC. Disclosure: All authors have declared no conflicts of interest.