Prevalence and clinical significance of pathogenic germline / mutations in Chinese non-small cell lung cancer patients.

OBJECTIVE

Germline alterations in the breast cancer susceptibility genes type 1 and 2, and , predispose individuals to hereditary cancers, including breast, ovarian, prostate, pancreatic, and stomach cancers. Accumulating evidence suggests inherited genetic susceptibility to lung cancer. The present study aimed to survey the prevalence of pathogenic germline mutations () and explore the potential association between and disease onset in Chinese advanced non-small cell lung cancer (NSCLC) patients.

METHODS

A total of 6,220 NSCLC patients were screened using capture-based ultra-deep targeted sequencing to identify patients harboring germline / mutations.

RESULTS

Out of the 6,220 patients screened, 1.03% (64/6,220) of the patients harbored the pathogenic , with mutations being the most pr edominant mutations (49/64, 76.5%). Patients who developed NSCLC before 50 years of age were more likely to carry ( = 0.036). Among the patients harboring classic lung cancer driver mutations, those with concurrent were significantly younger than those harboring the wild-type ( = 0.029). By contrast, the age of patients with or without concurrent was comparable to those of patients without the driver mutations ( = 0.972). In addition, we identified -mutant patients with concurrent g who showed comparable progression-free survival but significantly longer overall survival ( = 0.002) compared to -mutant patients with wild-type germline .

CONCLUSIONS

Overall, our study is the largest survey of the prevalence of pathogenic in advanced Chinese NSCLC patients. Results suggested a lack of association between germline status and treatment outcome of EGFR-TKI. In addition, results showed a positive correlation between pathogenic and an early onset of NSCLC.