The Prevalence, Distribution, and Clinicopathological Features of Seven Lung Cancer Actionable Driver Mutations in Taiwan.

Background: Efficient and affordable diagnosis, coupled with a clear understanding of driver gene prevalence, distribution, and clinicopathological features of driver genes, is crucial for lung cancer treatment and prevention. This study developed a cost-effective targeted sequencing assay for actionable driver mutation and investigated EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and HER2 in a southern Taiwanese lung cancer population.

Materials and methods: Two hundred and twenty-three lung cancer specimens from Chang Gung Memorial Hospital, Chiayi (2009-2020), were retrospectively analyzed.

Results: Among the 223 patients, the mutation frequencies detected by the optimized targeted sequencing assay were: EGFR 48.88%, KRAS 6.28%, PIK3CA 5.83%, NRAS and BRAF both 1.79%, MET 0.90%, and HER2 0.45%. While EGFR mutations in this cohort generally correlated with female sex, never-smoking status, and adenocarcinoma histology, some mutation subtypes deviated from this trend. Conversely, KRAS mutations showed no preference for gender, smoking, or histology, with G12C (42.86%) and G12D (28.57%) being predominant. PIK3CA mutations were more often observed in males and smokers. Concomitant driver mutations were common-except in KRAS and HER2-with prevalence rates of EGFR 5.50%, PIK3CA 61.54%, NRAS 25%, BRAF 50%, and MET 50%.

Discussion: The established actionable driver mutation targeted sequencing assay can cost-effectively facilitate treatment stratification for over 60% of lung cancer patients. The distinct features caused by mutations in the same gene or genes within similar pathways, coupled with the frequent occurrence of concomitant driver mutations, underscore the importance of economic molecular testing for both patient care and trial stratification.