Molecular characterization of lung adenocarcinoma from Korean patients using next generation sequencing

Autoři: You Jin Chun aff001;  Jae Woo Choi aff002;  Min Hee Hong aff001;  Dongmin Jung aff002;  Hyeonju Son aff004;  Eun Kyung Cho aff005;  Young Joo Min aff006;  Sang-We Kim aff007;  Keunchil Park aff008;  Sung Sook Lee aff009;  Sangwoo Kim aff004;  Hye Ryun Kim aff001;  Byoung Chul Cho aff001
Působiště autorů: Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea aff001;  Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea aff002;  Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea aff003;  Department of Biomedical Systems Informatics, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea aff004;  Division of Hematology-Oncology, Department of Internal Medicine, Gachon Medical School, Gil Medical Center, Incheon, Korea aff005;  Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea aff006;  Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea aff007;  Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea aff008;  Department of Hematology-Oncology, Inje University Haeundae Paik Hospital, Busan, Korea aff009
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224379


The treatment of Lung adenocarcinoma (LUAD) could benefit from the incorporation of precision medicine. This study was to identify cancer-related genetic alterations by next generation sequencing (NGS) in resected LUAD samples from Korean patients and to determine their associations with clinical features. A total of 201 tumors and their matched peripheral blood samples were analyzed using targeted sequencing via the Illumina HiSeq 2500 platform of 242 genes with a median depth of coverage greater than 500X. One hundred ninety-two tumors were amenable to data analysis. EGFR was the most frequently mutated gene, occurring in 106 (55%) patients, followed by TP53 (n = 67, 35%) and KRAS (n = 11, 6%). EGFR mutations were strongly increased in patients that were female and never-smokers. Smokers had a significantly higher tumor mutational burden (TMB) than never-smokers (average 4.84 non-synonymous mutations/megabase [mt/Mb] vs. 2.84 mt/Mb, p = 0.019). Somatic mutations of APC, CTNNB1, and AMER1 in the WNT signaling pathway were highly associated with shortened disease-free survival (DFS) compared to others (median DFS of 89 vs. 27 months, p = 0.018). Patients with low TMB, annotated as less than 2 mt/Mb, had longer DFS than those with high TMB (p = 0.041). A higher frequency of EGFR mutations and a lower of KRAS mutations were observed in Korean LUAD patients. Profiles of 242 genes mapped in this study were compared with whole exome sequencing genetic profiles generated in The Cancer Genome Atlas Lung Adenocarcinoma. NGS-based diagnostics can provide clinically relevant information such as mutations or TMB from readily available formalin-fixed paraffin-embedded tissue.

Klíčová slova:

Cancer genomics – Deletion mutation – Human genetics – Lung and intrathoracic tumors – Mutation databases – Next-generation sequencing – Nonsense mutation – Somatic mutation


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