KRAS mutations in patients with colorectal cancer in Libya.

Abstract

Large prospective clinical trials have demonstrated that colorectal cancers (CRCs) with wild-type KRAS respond favorably to anti-epidermal growth factor receptor treatment, thus making mutational analysis obligatory prior to treatment. In our study, frozen CRC tissues from Libyan patients were analyzed for KRAS and HRAS mutations in codons 12/13 by direct sequencing and the correlations with clinical and pathological parameters were investigated. A total of 34 CRC cases, comprising 19 men and 15 women (age range, 24-87 years), were subjected to systematic analysis for RAS mutations. Although HRAS mutations were not detected in any of the patients in the study group, KRAS codon 12/13 mutations were present in 38.2% (13/34) of the patients. The frequent types of codon 12 mutations were glycine to aspartate (G12D, 46.1%); glycine to valine (G12V, 30.8%) and glycine to cysteine (G12C, 15.4%), while the codon 13 mutations were glycine to aspartate (G13D, 7.7%). G→A mutations occurred in 53.8% (7/13) of the patients, while G→T mutations occurred in 46.2% (6/13) of the patients. Mutations occurred at the first base of codon 12 or 13 in 2/13 (15.4%) and at the second base in 11/13 (84.6%) patients. There was no significant association between clinicopathological characteristics and KRAS mutation status, except the site of the tumors harboring KRAS mutations, which was as follows: The frequency was higher among tumors located in the left colon (8/13, 61.5%) compared to other sites (P=0.027). KRAS mutations were correlated with advanced age, with 10/13 being aged >50 years and affected 8/15 female patients (53%) compared with 5/19 male patients (26%). The highest frequency of KRAS mutations was observed in highly differentiated CRCs (8/13).