Comparison of KRAS mutation analysis of primary tumors and matched circulating cell-free DNA in plasmas of patients with colorectal cancer

Abstract Colorectal cancer (CRC) patients with KRAS mutations do not benefit from epidermal growth factor receptor (EGFR) targeted therapy. In clinical practice, identifying patients with KRAS mutations is critical prior to EGFR targeting therapy, and gene testing is generally performed using the DNA extracted from tumor tissue. The aim of this study was to compare the presence of KRAS mutations in circulating cell-free DNA (cfDNA) and primary tumor tissue using a peptide nucleic acid mediated polymerase chain reaction. We extracted and analyzed the DNA from plasmas and corresponding primary tumor samples from 52 patients with CRC. The results demonstrated that the detection rate of KRAS sequence variations was 50% (26 of 52) in plasma samples and 28.8% (15 of 52) in resected primary tumor tissue samples. The majority of KRAS mutations detected in tumors were also found in matched plasma specimens with an agreement rate of 78.8%. Eleven plasma cfDNA were found positive for KRAS mutation but not in their corresponding tissue. In conclusion, our results suggest that circulating cfDNA provides a better representation of the malignant disease as a whole and could be a reliable source of diagnostic DNA to replace the tumor tissue in a diagnostic setting.