KRAS mutations and subtyping in colorectal cancer in Jordanian patients

Abstract

Abstract. 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 wild -type 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.

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

“…A study by Siraj et al reported a BRAF mutation rate of 2.5% in a Saudi Arabian population (19). The rate of KRAS in Arab population from outside the Arab Gulf population has been reported, Elbjeirami et al reported a KRAS mutation rate of 44% in a Jordanian population (20). The ratio of patients with mutated versus wild-type KRAS in the Jordanian study was similar to that reported in Western countries.…”

“…The rate of these mutations in Arab patients with CRC is not well defined (9). The evaluations of the rates of these mutations in Arab population with CRC have been limited to few mutations including KRAS and BRAF (19,20).…”

Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes

“…The prevalence of mutated K-ras in our study was 42% in patients who were mostly in stages II-IV of mCRC, and is broadly concordant with data from other Middle Eastern countries and the western world, within the limitations of comparison. The finding that about nine in ten mutations were in codon 12 was also similar to the findings from other countries in the region (Abubaker et al, 2009;Elbjeirami and Sughayer, 2012;Gumus et al, 2013;Marchoudi et al, 2013;Baskin et al, 2014) and elsewhere (Karapetis et al, 2008;Zalis et al, 2009;Gil Ferreira et al, 2014). We found that mutant K-ras tumors were more likely to be present in patients in an advanced stage of the disease compared to those with the wild-type K-ras tumors.…”

“…Previous studies from the Middle East (or in the Arab population) that enrolled a relatively large number of patients and included patients with different stages of the disease, reported K-ras mutation rates of 28-56% in Saudi Arabia (Abubaker et al, 2009;Zahrani et al, 2014;Beg et al, 2015;Dallol et al, 2016), 33-45% in Turkey (Gumus et al, 2013;Baskin et al, 2014), and 33-44% in Jordan (Elbjeirami and Sughayer, 2012;Gumus et al, 2013). Lower mutation rates were observed in countries to the west of Saudi Arabia, such as Egypt (11-18%) (Soliman et al, 2001;Gumus et al, 2013), and Morocco (24%) (Marchoudi et al, 2013).…”

Molecular Analysis of KRAS Mutation Associated with Colorectal Cancer in Iraqi Patients

“…Literatures regarding colorectal cancer in Arabian countries (Wafa and Maher, 2012;Abulkair et al, 2016) studied KRAS mutation at codon 12 and 13 only, but non of these articles detailed the full spectrum of SNPs and their clinical significant as whole.…”