KRAS G12C Mutations in Asia: a Landscape Analysis of 11,951 Chinese Tumor Samples

Background: Kirsten rat sarcoma vial oncogene () is one of the most prevalent oncogenes in multiple cancer types, but the incidence is different between the Asian and non-Asian populations. The recent development of G12C targeting drug has shown great promise. It is thus important to understand the genomic landscape of G12C in a specific population.

Methods: Sequencing data of 11,951 tumor samples collected from 11/2016 to 7/2019 from multiple centres in China were analyzed for mutation status. Concomitant genomic aberrations were further analyzed in tumors with G12C mutations, which were sequenced with comprehensive cancer panel including over 450 cancer-related genes. Smoking status and its correlation with were analyzed in 2,235 lung cancer cases within this cohort.

Results: KRAS mutations were identified in 1978 (16.6%) patient samples. Specifically, G12C accounted for 14.5% (n=286) of all mutations. G12C was most commonly seen in lung cancer (4.3%), followed by colorectal cancer (2.5%) and biliary cancer (2.3%). Almost all patients (99.6%) with G12C mutations had concomitant genomic aberrations. These were most commonly associated with the RAS/RTK pathway including and mutations. Moreover, mutation was positively correlated with smoking status in lung adenocarcinomas.

Conclusions: The overall incidence of G12C mutations remains low in the Chinese population. The most common tumor types harboring G12C mutations are in patients suffering from lung, colorectal and biliary cancers.