Common KRAS and NRAS gene mutations in sporadic colorectal cancer in Northeastern Iranian patients

Objectives: Mutation analysis of the Epidermal Growth Factor Receptor downstream has been a main part of colorectal carcinoma evaluation. Large prospective clinical trials have shown only colorectal cancer (CRC) with wild-type KRAS and NRAS responds to anti-Epidermal Growth Factor Receptor treatment. Hence, mutation analysis is necessary prior to treatment. It is essential to conduct studies to learn about the mutation signature of such tumors. The aim of this study was to evaluate the frequency of hotspot mutations in KRAS and NRAS genes in Iranian CRC patients and to explore their correlations with clinicopathologic parameters. Methods: We detected mutations in exon 2 (codons 12 and 13) of the KRAS and NRAS genes using high resolution melting analysis, Intplex design and Sanger sequencing in 87 Iranian CRC patients. Genomic DNA was isolated from fresh tissue samples of CRC patients. Results: From 87 eligible cases, 51 were male and 36 were females. KRAS mutations in codons 12 and 13 were present in 28.7% of all analyzed CRCs. Our findings suggested that the tumors with KRAS mutations are not with well- and moderately differentiated tumors compared to poorly differentiated tumors (P value = 0.32). The most frequent types of mutations were glycine to aspartate on codon 12 (p.G12D), and glycine to aspartate on codon 13 (p.G13D). No mutation was found in the NRAS gene in our patients. Conclusions: Based on this study, the frequency of KRAS mutations seems to be in the spectrum of frequencies of other countries such as China, Japan, India, USA, France, and Germany and NRAS was similar to the West of Iran.