Actionable Mutation Profiles of Non-Small Cell Lung Cancer patients from Vietnamese population

Abstract

Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.

Figure 1

The mutation composition in six major driver genes in 350 Vietnamese NSCLC patients. (A) Prevalence of mutations in 6 major driver genes determined by targeted capture sequencing. Cases with mutations occurring in more than one driver gene were counted as “co-mutation”. (B) Mutation frequency in cases harbouring co-mutations.

Figure 2

Distribution of mutation subtypes across 6 driver genes in Vietnamese NSCLC. (A–F) The mutation frequencies in particular subtypes of EGFR (A), KRAS (B), BRAF (C), NRAS (D), ALK (E) and ROS1 (F) genes were calculated as percentage of mutant cases in the total number of cases carrying mutations in the corresponding driver gene.

Figure 3

Comparison of driver gene mutation frequencies between Vietnamese NSCLC cohort with Caucasians and East Asians. Mutation frequency of each driver gene in the Vietnamese cohort was calculated among 220 patients with adenocarcinoma (AC) in late stages (III-IV) taking into account cases with co-mutation. For the Caucasian cohort, data were obtained from the MSK-IMPACT cohort (764 lung cancer cases with AC subtypes in metastatic stages (III-IV), Asian patients were excluded). For East Asia cohort, data we retrieved from a recent report profiling a similar panel of driver mutations in a Chinese cohort of 361 patients with AC in late stages (III-IV). NT: mutations were not tested.