A comparative genomics analysis of lung adenocarcinoma for Chinese population by using panel of recurrent mutations

Previous studies have demonstrated that Chinese lung adenocarcinoma (LUAD) patients have unique genetic characteristics, however, the specific genomic features relating to the development and treatment of LUAD in the Chinese population are not fully understood. Here, we applied the ultra-deep targeted sequencing to 66 Chinese LUAD samples, accompanied by comparative analysis with 162 Caucasian LUAD in The Cancer Genome Atlas. We focused on the 68 recurrently mutated genes and results revealed that the panel-based tumor mutational burden (pTMB) is significantly higher in the Chinese LUAD (P=0.0017). Additionally, the percentage of smoking-associated C>A transversion is significantly lower in Chinese LUAD (15.5%vs. 39.7%, P=5.69×10⁻²⁷), while C>T transition is more frequent in Chinese LUAD (35.8%vs. 25.7%, P=2.67×10⁻⁵), which indicated the ethnic difference in mutation types. Notably, novel driver genes (GNAS and JAK1) that are peculiar to Chinese LUAD were identified, and a more convergent distribution of mutations was observed in the Chinese cohort (P=0.012) compared with scattered mutations in Caucasian LUAD. Our results present a distinct genomic profile of Chinese LUAD compared to Caucasians LUAD and elucidate the ethnic difference in mutation distribution besides the type and rate.