Profiling Oncogenic Germline Mutations in Unselected Chinese Lung Cancer Patients

• DOI: 10.3389/fonc.2021.647598
• Publication Date: 2021-04-07T06:15:02Z
• Authors: Jie Yang; Hefei Li; Ben Li; Wei Li; Qiang Guo; Ling Hu; Zizheng Song; Bin Zhou
• Keywords: 03 medical and health sciences; variants of uncertain significance; 0302 clinical medicine; germline mutation; Oncology; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; oncogenic gene; likely pathogenic/pathogenic variant; lung cancers; RC254-282; 3. Good health

Emerging evidence has suggested that inherited factors are also involved in lung cancer development. However, most studies focused on well-elucidated predisposition genes, the majority of which tumor suppressor genes. The profile germline mutations oncogenic driver genes remains unrevealed, might provide potential clinical implications for management.Sequencing data from 36,813 unselected patients who underwent somatic mutation profiling were retrospectively reviewed. All recruited had matched white blood cell samples sequenced parallel using a capture-based panel including eight key (epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), MET proto-oncogene, tyrosine (MET), Kirsten rat sarcoma viral oncogene homolog (KRAS), Erb-B2 2(ERBB2), ROS proto-oncogene 1, (ROS1), ret (RET), and B-Raf serine/threonine (BRAF)). Likely pathogenic/pathogenic (LP/P) variants called according to classification criteria American College Medical Genetics Genomics. Variants uncertain significance (VUS) located domains occurring recurrently (n ≥3) included further analyses.Seven different LP/P EGFR, MET, or RET identified 0.03% = 14) 25 VUS seven (except KRAS) found with prevalence 0.3% 117).Collectively, frequently seen ROS1 31, 0.084%), followed by 23, 0.062%), EGFR 22, 0.06%), ALK 0.06%) 17, 0.046%). fell commonly 10, 72%) 26%), respectively. Of 10 mutation, 70% acquired exon21 p.L858R exon19 deletion at baseline; while three pathogenic displayed distinct baseline profiles rare KRAS exon2 p.G12C. We discovered 11 occurred somatically, four VUS.We present first study systemically characterize large cohort cancers.