Qiuhua Deng1, Yuan Qiu2, Junmei Jia3, Hailing Tang1, Liping Liu1, Liyan Huang1, Dongyun He2, Xiaomeng Dong4, Haihong Yang2. 1. The Center for Translational Medicine, National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China. 2. Department of Thoracic Oncology, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou 510120, China. 3. Department of Oncology, First Affiliated Hospital of Shanxi Medical College, Taiyuan 030001, China. 4. Shanghai Tongshu Biotechnology Co., Ltd, Shanghai 200120, China.
Abstract
BACKGROUND: Genetic alteration profile of epidermal growth factor receptor (EGFR) mutant resected non-small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out. METHODS: Clinicopathological and follow-up information were collected for 99 EGFR-mutant resected NSCLC. Tumor sections were collected for genetic alteration detection. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations within each sample using a 285-gene panel on the Ion Torrent platform. RESULTS: Concurrent driver gene mutations were detected in 86 participants. Adjuvant therapy was a positive factor in disease-free survival (DFS) period, and patients receiving tyrosine kinase inhibitors (TKIs) gained the longest DFS. A total of 34 concurrent mutant driver genes were found. The median number of mutated driver genes for each sample was 2 (range, 0-12). TP53 and NOTCH1 were the most frequent concurrent mutant driver genes with rates of 53.54% and 25.25% respectively. The number of concurrent mutant genes did not have a significant effect on recurrence. Multivariable analysis found that mutations of ATM (P=0.021), KIT (P=0.002), FGFR2 (P<0.001), MET (P=0.015), PDGFRA (P=0.042), RB1 (P=0.006), and wildtype NOTCH1 (P=0.032), ERBB4 (P=0.012), FGFR3 (P=0.035) were independent risk factors for the recurrence of resected EGFR mutant NSCLC. CONCLUSIONS: TP53 and NOTCH1 was the most common concurrent mutant driver gene. Mutations of ATM, KIT, FGFR2, MET, PDGFRA, RB1, and wildtype NOTCH1, ERBB4, FGFR3 were independent risk factors for the recurrence of resected EGFR mutant NSCLC. 2019 Translational Lung Cancer Research. All rights reserved.
BACKGROUND: Genetic alteration profile of epidermal growth factor receptor (EGFR) mutant resected non-small cell lung cancer (NSCLC) and its relationship with clinical outcomes remains to be illustrated and genetic biomarkers that can predict recurrence need to be figured out. METHODS: Clinicopathological and follow-up information were collected for 99 EGFR-mutant resected NSCLC. Tumor sections were collected for genetic alteration detection. Targeted next-generation sequencing (NGS) was performed to detect somatic mutations within each sample using a 285-gene panel on the Ion Torrent platform. RESULTS: Concurrent driver gene mutations were detected in 86 participants. Adjuvant therapy was a positive factor in disease-free survival (DFS) period, and patients receiving tyrosine kinase inhibitors (TKIs) gained the longest DFS. A total of 34 concurrent mutant driver genes were found. The median number of mutated driver genes for each sample was 2 (range, 0-12). TP53 and NOTCH1 were the most frequent concurrent mutant driver genes with rates of 53.54% and 25.25% respectively. The number of concurrent mutant genes did not have a significant effect on recurrence. Multivariable analysis found that mutations of ATM (P=0.021), KIT (P=0.002), FGFR2 (P<0.001), MET (P=0.015), PDGFRA (P=0.042), RB1 (P=0.006), and wildtype NOTCH1 (P=0.032), ERBB4 (P=0.012), FGFR3 (P=0.035) were independent risk factors for the recurrence of resected EGFR mutant NSCLC. CONCLUSIONS: TP53 and NOTCH1 was the most common concurrent mutant driver gene. Mutations of ATM, KIT, FGFR2, MET, PDGFRA, RB1, and wildtype NOTCH1, ERBB4, FGFR3 were independent risk factors for the recurrence of resected EGFR mutant NSCLC. 2019 Translational Lung Cancer Research. All rights reserved.
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