Frequency and Clinicopathological Characteristics of Patients With KRAS/BRAF Double-Mutant Colorectal Cancer: An In Silico Study

KRAS and BRAF mutations are currently thought to be mutually exclusive as their co-occurrence is extremely rare. Therefore, clinicopathological and molecular characteristics of colorectal carcinoma with KRAS/BRAF double mutations are unclear. We aimed to investigate the frequency and clinicopathological characteristics of double-mutant colorectal carcinoma and its differences from KRAS/BRAF single-mutant colorectal carcinoma using bioinformatics tools. We estimated the KRAS/BRAF double mutation frequency in the whole exon and coding sequences via bioinformatic analyses of three datasets from cBioPortal. We compared the clinicopathological characteristics, microsatellite instability status, BRAF classification, and tumor mutation burden of patients harboring the double mutants with those of patients harboring KRAS or BRAF single mutations. We integrated three large datasets and found that the frequency of the KRAS/BRAF double mutation in the dataset was 1.2% (29/2347). The double mutation occurred more frequently in males, with a slightly higher occurrence in the right side of the colon. Sex, histological type, histological grade, microsatellite instability, and tumor mutation burden of the patients harboring KRAS-mutant, BRAF-mutant, and double-mutant colorectal carcinoma varied significantly. The frequency of double-mutant colorectal carcinoma was 60 times higher than that previously reported. Significantly fewer double-mutant colorectal carcinoma cases were classified as BRAF class 1 and more were classified as unknown. Our findings indicate that the biological characteristics of double-mutant tumors are different from those of single-mutant tumors.