role of Kras mutations and MSI status in diagnosis of colorectal cancer

ABSTRACT

The aim of the current investigation was to examine the profile of Kras mutations accompanied with MSI [microsattelite instability] status in polyps and colorectal carcinoma tissues in an Iranian population. Kras mutations in colorectal cancer cause resistance to anti-Epidermal Growth Factor Receptor [EGFR]. So it can be considered as a true indicator of EGFR pathway activation status. Kras mutations can be detected in approximately 30% to 40% of all patients with colorectal cancer. The most hot spot of the gene is located in exons 2 and 3. In this study we examined exons 2 and 3 Kras gene using polymerase chain reactions and subsequent sequencing of the exons in 95 patients with sporadic colorectal cancer including 48 tumors and 47 polyps. This study was performed using biopsy samples from the patients. We sequenced the Kras gene in a panel of human colorectal tumors and polyps in addition to detecting MSI status using fluorescent technique. We could detect 6 mutations in tumors including 5 mutations in codon 12 and one mutation in codon 13. Moreover, in polyps 2 mutations were determined in codon 13 and one in codon 12. Microsatellite instability assay revealed the presence of 5 and 6 MSI in tumors and polyps, respectively. Among the MSI mononucleotide markers, NR-21 marker demonstrated the most frequency [60%] in the both groups. Our findings showed that probably the profile of mutations in tumors is not entirely compatible with the pattern of mutations in polyps. However, just one of the mutations, Gly12Asp, was similar in both groups