Correlation between KRAS, NRAS and BRAF mutations and tumor localizations in patients with primary and metastatic colorectal cancer

INTRODUCTION: Detection of abnormalities in the KRAS, NRAS and BRAF genes is extremely important for proper qualification of colorectal cancer (CRC) patients for therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies. However, data about prevalence of mutations in these genes, in different localizations of CRC tumors, are limited. MATERIAL AND METHODS: We examined the frequency of mutations in the KRAS, NRAS and BRAF genes in 500 Caucasian CRC patients (200 women and 300 men, median age 66 years). DNA was isolated from formalin-fixed, paraffin-embedded (FFPE) tissues using a Qiagen QIAamp DNA FFPE-kit. Analysis of mutations was carried out using the KRAS/BRAF, NRAS and BRAF Mutation Analysis Kit for Real-Time PCR (EntroGen) with the Cobas 480 real-time PCR apparatus (Roche Diagnostics). RESULTS: KRAS mutations were detected in 190 (38%) patients, NRAS mutations in 20 (4%) patients, and BRAF mutations in 24 (4.8%) patients. There were no associations between age of CRC patients and frequency of KRAS, NRAS and BRAF gene mutations. These mutations were significantly more often diagnosed in women (55.5%) than in men (41%, p < 0.005). Tumors of the rectum and sigmoideum were the most often observed in both groups of CRC patients – with and without KRAS, NRAS and BRAF gene mutations. However, transverse colon, ascending colon and cecum cancers were the most often affected by mutations. CONCLUSIONS: Our study showed that the occurrence of mutations in the KRAS, NRAS and BRAF genes is not accidental and depends on the location of CRC tumors.