Characterization of driver mutations in Chinese non-small cell lung cancer patients using a novel targeted sequencing panel

Abstract

Background: The identification of driver mutations has greatly promoted the precise diagnosis and treatment of non-small cell lung cancer (NSCLC), but there is lack of targeted sequencing panels specifically designed and applied to Chinese NSCLC patients. This study aimed to design and validate of a novel sequencing panel for comprehensive characterization of driver mutations in Chinese NSCLC patients, facilitating further exploration of downstream pathway alterations and therapeutic utility.Methods: A novel target sequencing panel including 21 driver genes was designed and examined in a cohort of 260 Chinese NSCLC patients who underwent surgery in Peking Union Medical College Hospital (PUMCH). Genetic alterations were identified and further analyzed for driver mutations, downstream pathways and therapeutic utilities. Results:The most frequently identified driver mutations in PUMCH NSCLC cohort were on genes TP53 (28%), EGFR (27%) and PIK3CA (19%) for lung adenocarcinoma (LUAD), and TP53 (41%), PIK3CA (14%) and CDKN2A (13%) for lung squamous cell carcinoma (LUSC), respectively. Downstream pathway analysis revealed common pathways like G1_AND_S1_PHASES pathway were shared not only between LUAD and LUSC patients, but also among three different NSCLC cohorts, while other pathways were subtypespecific, like the unique enrichment of SHC1_EVENT_IN_EGFR_SIGNALING pathway in LUAD patients, and P38_ALPHA_BETA_DOWNSTREAM pathway in LUSC patients, respectively. About 60% of both LUAD and LUSC patients harbored driver mutations as sensitive biomarkers for different targeted therapies, covering not only frequent mutations like EGFR L858R mutation, but also rare mutations like BRAF D594N mutation. Conclusions:Our study provides a novel target sequencing panel suitable for Chinese NSCLC patients, which can effectively identify driver mutations, analyze downstream pathway alterations and predict therapeutic utility. Overall it is promising to further optimize and apply this panel in clinic with convenience and effectiveness.