Masayuki Nagahashi1, Seijiro Sato2, Kizuki Yuza3, Yoshifumi Shimada3, Hiroshi Ichikawa3, Satoshi Watanabe4, Kazuki Takada5, Tatsuro Okamoto6, Shujiro Okuda7, Stephen Lyle8, Kazuaki Takabe9, Masanori Tsuchida2, Toshifumi Wakai3. 1. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. Electronic address: mnagahashi@med.niigata-u.ac.jp. 2. Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 3. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 4. Department of Respiratory Medicine and Infectious Disease, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 5. Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. 6. Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan. 7. Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 8. University of Massachusetts Medical School, Worcester, Massachusetts. 9. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Surgical Oncology, Breast Surgery, Roswell Park Cancer Comprehensive Cancer Center, Buffalo, New York; Department of Surgery, University at Buffalo Jacobs School of Medicine and Biosciences, The State University of New York, Buffalo, New York; Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan; Department of Surgery, Yokohama City University, Yokohama, Japan.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 < 0.05). Notably, no EGFR mutation was observed in patients with TMB-H. Eight of 10 (80%) patients with TMB-H had recent smoking history, whereas only 17 of 90 (19%) patients with TMB-L had recent smoking history (P < 0.001). CONCLUSIONS: We found that TMB-H is associated with smoking history, whereas TMB-L is associated with the common driver mutations in lung adenocarcinoma, which may impact treatment strategies for these patients.
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 < 0.05). Notably, no EGFR mutation was observed in patients with TMB-H. Eight of 10 (80%) patients with TMB-H had recent smoking history, whereas only 17 of 90 (19%) patients with TMB-L had recent smoking history (P < 0.001). CONCLUSIONS: We found that TMB-H is associated with smoking history, whereas TMB-L is associated with the common driver mutations in lung adenocarcinoma, which may impact treatment strategies for these patients.
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