Key Points
• In the current study, Chinese researchers mined sequenced data from 36,813 unselected lung cancer patients who were profiled for somatic mutations. They looked at eight lung cancer genes including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), MET proto-oncogene, receptor tyrosine kinase (MET), Kirsten rat sarcoma viral oncogene homolog (KRAS), Erb-B2 receptor tyrosine kinase 2(ERBB2), ROS proto-oncogene 1, and receptor tyrosine kinase (ROS1).
• The authors of this retrospective study stressed that there is a paucity of well-elucidated research on germline mutations in oncogenic driver genes. Such studies could improve the management of lung cancer.
• Seven likely pathogenic/pathogenic variants in EGFR, MET, or RET were noted in % of lung cancer patients, as well as 25 different variants of uncertain significance (VUS) in the kinase domains of seven driver genes with a prevalence of 0.3%. Intriguingly, KRAS was not found, with most variants being EGFR (72%) and ROS1 (26%).
• “The vast majority of EGFR or MET germline mutation carriers in our study harbored the common EGFR driver mutation exon19 deletion or exon21 p.L858R, while RET germline mutation carriers displayed distinct baseline somatic profiles of rare EGFR mutation or KRAS exon2 p.G12C, which might indicate distinctive mechanisms underlying tumorigenesis in RET–mutant patients,” the authors wrote.
• “[W]e present the first study to systemically characterize the germline mutation in oncogenic driver genes in a large cohort of unselected patients with lung cancer. Our findings may provide potential clinical implications for lung cancer management,” the authors concluded.