Germline mutations among patients with non-small cell lung cancer.

e20527 Background: Lung cancer is currently a leading cause of cancer-associated mortality worldwide. Germline mutations potentially predisposing patients to lung cancer have not been systematically defined. In this study, we sought to determine the prevalence of pathogenic/likely pathogenic (P/LP) germline mutations in patients with NSCLC. Methods: A total 1562 patients with NSCLC were included in this study. Leukocyte DNA was extracted and detected were using next generation sequencing technology. Allele frequencies were compared with publicly available database. Interpretation of sequence variations was classified according to the American College of Medical Genetics and Genomics guidelines. Results: Overall, median age at testing of individuals was 63 years (range 12 to 91). The majority of individuals tested were male (56.15%, 877/1562). of 1562 NSCLC, P/LP mutations were identified in 94 (6.02%) in 42 Cancer Susceptibility genes. No individuals carried more than 1 germline variant. The most common P/LP mutations in genes were MUTYH (n = 11, 0.70%), TP53 (n = 10, 0.64%), BRCA2 (n = 8, 0.51%), PALB2(n = 5, 0.32%), PTEN(n = 4, 0.26%), BLM(n = 3, 0.19%), WRN(n = 3, 0.19%), and ATR, BRCA1 and BRIP1 (n = 2, 0.13% each). Twenty eight patients were carried germline mutations in homologous recombination repair(HRR), including BRCA2 (8), PALB2 (5), PTEN (4), BRCA1 (2), BRIP1 (2), CHEK2 (2), FANCA (2), ATM (1), RAD51B (1), RAD54L(1). Of note, the clinical features of patients with HRR mutations were not young adult (median age [range], 57 [41-80] years). Conclusions: Of 1562 patients with NSCLC, 94 (6.02%) had germline mutations and 27 (1.73%) had mutations in HRR genes. The presence of HRR germline mutations could guide cancer screening for patients and their families and serve as predictive biomarkers of response to targeted or immunotherapies. More extensive germline testing in NSCLC should be considered.