Prevalence and Pattern of KRAS and NRAS Mutations in Colorectal Cancer: A Libyan Retrospective Study

Abstract

About 53% of colorectal cancer (CRC) patients were reported to have the Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations. These mutations in the KRAS gene are able to render the targeted therapy agents such as monoclonal antibodies cetuximab and panitumumab ineffective against the epidermal growth factor receptor (EGFR). Disparities between regions have been described in the literature regarding these mutations. This is an original investigation aimed at characterising the frequency and patterns of KRAS mutations in Libyan patients with colorectal cancer. Tissue samples of 79 cases of colorectal cancer were analysed for KRAS and NRAS mutations. Of these, 44 (55.7%) reported positive. In the KRAS positive patients, there were 23 (52.3%) males and 21 (47.7%) females. Majority of cases (77.0%) were with point mutations in codon 12 whereas (7%) had a single mutation in codon 13. There were 3 patients showing mutation in codon 61 with two nucleotide changes whereas the last 4 patients exhibited three nucleotide changes in codon 146. The more prevalent KRAS mutation was p.Gly12Val (c.35G>T) (29.5%), followed by p.Gly12Asp (c.35G>A) (25%). The G>A transitions in both codons 12 and 13 accounted for 41.0% of all the mutant KRAS cases. The transversions G>T in codon 12 alone forms 38.6% of the total KRAS mutation. The p.Gly12Val (c.35G>T) mutation had the highest frequency in both males (26.1%) and females (33.3%). Same tendency also was seen in p.Gly12Asp (c.35G>A) mutation but to lesser extent with (30.4%) in male and (19%) in female. Interestingly, the p.Gly13Asp (c.38G>A) mutation had pure appearance in male. Multiple mutations in the same individual were detected in 7 patients in this cohort (16%). Our results showed a relatively higher prevalence of KRAS mutation in Libyan patients compared to other analogous data observed worldwide. Two samples only out of 29 showed mutation in NRAS codon 61. Being a retrospective study with small sample size were the main limitations for this study. Thus we recommend that conduction of larger studies is needed in the future.