Common driver mutations and smoking history affect tumor mutation burden in lung adenocarcinoma

• Published in: The Journal of surgical research 2018-10, Vol.230, p.181-185
• Main Authors: Nagahashi, Masayuki, Sato, Seijiro, Yuza, Kizuki, Shimada, Yoshifumi, Ichikawa, Hiroshi, Watanabe, Satoshi, Takada, Kazuki, Okamoto, Tatsuro, Okuda, Shujiro, Lyle, Stephen, Takabe, Kazuaki, Tsuchida, Masanori, Wakai, Toshifumi
• Format: Article
• Language: English
• Subjects: Adenocarcinoma of Lung - genetics; Anti-PD-1; Biomarkers, Tumor - genetics; Carcinogenesis - genetics; Genomics - methods; High-Throughput Nucleotide Sequencing; Humans; Immune checkpoint inhibitors; Lung adenocarcinoma; Lung Neoplasms - genetics; Mutation; Next-generation sequencing; Smoking - epidemiology; Tumor mutation burden
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2018.07.007

Recent progress in genomic analysis using next-generation sequencing technology has enabled the comprehensive detection of mutations and tumor mutation burden (TMB) in patients. A high TMB (TMB-H) tumor is defined as one with high somatic mutational rates, which correlates with clinical responses to certain treatments such as immunotherapies. We determined TMB in lung adenocarcinoma and clarified the characteristics of patients with TMB-H in relation to common driver mutations and smoking history. Genomic aberrations and TMB were determined in Japanese patients with lung adenocarcinoma (n = 100) using next-generation sequencing of 415 known cancer genes. TMB-H was defined as > 20 mutations per megabase (Mb) of sequenced DNA. The median TMB was 13.5 (5-33) mutations/Mb. Ten of 100 (10%) patients showed TMB-H, and the others showed low TMB (TMB-L). Only two of 10 (20%) patients with TMB-H had one of the common driver mutations (ALK and ERBB2 mutation), whereas 57 of 90 (63%) patients with TMB-L had one of the driver mutations, including ALK, EGFR, ERBB2, ROS, RET, and MET (P