The frequency of ctDNA with KRAS, NRAS, and BRAF mutations in colorectal cancer is associated with the mutation site

Abstract

Abstract Early prediction of metastatic risk after tumor resection for colorectal cancer (CRC) is critical to improve treatment outcomes. Although circulating tumor DNA (ctDNA) is an important biomarker in CRC patients, methods and cutoff values have not been clearly established. In this study, we examined the relationship between mutatnt allele frequency (MAF) and the genetic mutation site and factors that influence the prediction of recurrence by ctDNA. This study included 422 CRC patients who underwent surgery. ctDNA was sampled from blood samples of 102 CRC patients with KRAS, NRAS and BRAF mutation and analyzed using the digital polymerase chain reaction system. Preoperative, postoperative day 1, postoperative day 7, and postoperative day 30 MAF was examined for each gene mutation sites. Kruskal–Wallis test revealed significant differences in MAF between mutated codon sites at all MAF assessment times (p < 0.001). The MAF values of KRAS codon 146 at all time points were significantly higher than for the other mutation sites. This study revealed that MAF values differed significantly depending on the site of mutation, even for the same gene. These results indicate that MAF cutoff values need to be established not only for each gene but also for each mutation site.