Landscape of RAS Variations in 17,993 Pan-cancer Patients Identified by Next-generation Sequencing

RAS family genes (HRAS, KRAS and NRAS) were frequently observed in several tumors. The expression of constitutively active RAS proteins mediated by RAS variations promote the development of tumors. KRAS is an important prognostic and drug resistance biomarker. It would also be a promising drug target. Several trials which evaluating the efficacy of RAS G12C inhibitor in solid tumors are initiated. Herein, we analyzed the alterations status of KRAS/NRAS/HRAS across diverse solid tumors. The sing nucleotide variants (SNV) and copy number variants (CNV) data of 17993 Chinese patients from 22 types of cancer were obtained in our database. Genomic profiling of DNA was performed through a next-generation sequencing on tissue. Only the pathogenic mutations and likely pathogenic mutations in clinical significance were rolled into our analysis. Among 17993 pan-cancer patients, the total RAS variants frequency was 22.58%. KRAS was the most frequently altered, followed by NRAS and HRAS. For the SNV, KRAS were most commonly found in pancreas cancer, intestine cancer and colorectal cancer. Further analysis among KRAS SNV patients showed that the mutation frequency of KRAS G12C, G12D, G12R, and G12V was 1.81%, 6.81%, 0.69% and 4.25%, respectively. A total of 21 in 22 types of solid tumors had KRAS G12C/D/R/V pathogenic or likely pathogenic mutation, which occurred most frequently in colorectal cancer, pancreas cancer and lung cancer. Our results suggested that a variety of solid tumors may harbor KRAS G12C/D/R/V mutation. These patients may benefit from KRAS inhibitors.