Concordance of KRAS, NRAS, BRAF, PIK3CA genes mutation status between the primary tumor and metastases in patients with colorectal cancer

Introduction. The aim of this study was to find factors associated with the discordance of KRAS, NRAS, BRAF, PIK3CA mutation status between the primary tumors and metastases in patients with CRC. Patients and methods. We performed DNA melting analysis with TaqMan probes and following Sanger sequencing to detect mutation hot-spots in KRAS exons 2 and 3, NRAS exons 2 and 3, BRAF exon 15, PIK3CA exons 9 and 20 in 148 tumor tissues in 65 patients (65 patients with primary tumors and 83 patients with metastases). Results. Mutations in KRAS, NRAS, PIK3CA and BRAF genes were detected in 43.1 %, 3.1 %, 13.8 % and 3.1 %, patients with primary tumors respectively. Discordance of mutation status of genes was identified in 29.2 % of patients: 16.9 % in KRAS, 3 % in NRAS, 12.3 % in PIK3CA and 3 % BRAF status. The discordance of mutation status of genes was detected in cases of brain metastases (p=0.02) and peritoneal metastases (p=0.02). With the increase of period from removal of the primary tumor and metastases, the incidence rate of changes in the mutational status of the genes also increased. Conclusion. Changes of the mutational status of genes, especially in the long course of the disease, raises the question of necessity of repeating biopsies in cases of the progression of the disease with the aim to identify the mutantional status of the tumor which we are treating at the moment.