KRAS mutations and subtyping in colorectal cancer in Jordanian patients

Colorectal cancer (CRC) is one of the most common malignancies in the Western world and Jordan. v-Ki-ras2 Kirsten rat sarcoma (KRAS) mutations represent an early event in the development and progression of CRC. Previous studies have demonstrated that KRAS mutations serve as a predictor of response to EGFR-targeted therapies for patients with metastatic CRC. The aim of this study was to determine the portion of CRC patients with wildtype KRAS status and molecular subtypes of KRAS mutations in Jordan as compared with other countries. DNA was isolated from 100 consecutive colorectal carcinoma specimens from patients who underwent surgical resection or colonoscopic biopsies of colorectal tumors and had developed metastatic disease. KRAS mutations were detected by hybridization-based strip assay as well as RT-PCR-based assay and confirmed by standard Sanger sequencing of codon 12 and 13 of exon 1 of the KRAS gene. Among 100 tested patients, 56% had a wt-KRAS genotype and 44% had a mutated KRAS genotype. The pGly12Asp was the most commonly detected mutation (54.5%). KRAS mutations were independently associated with patient age, gender and tumoral variables. The ratio of mutated versus wt-KRAS patients in this study is similar to those reported in Western countries but contrasts to neighboring Middle Eastern countries. Colorectal carcinoma cases from Jordan had higher KRAS mutation frequencies compared with other Middle Eastern countries which is likely to reflect different molecular pathogenesis and environmental exposures.