Frequency of NRAS Gene Mutation in Wild Type KRAS and BRAF Colorectal Cancers; a Single Center Study

Abstract

BACKGROUND Incidence of colorectal cancer is increasing in countries such as Iran. Molecular biomarkers play very important role in the diagnosis, treatment, and prognosis of this cancer. Mutation in the RAS family (including KRAS and NRAS) is one of these important molecular biomarkers, which should be tested before starting treatment with anti-EGRF (Epidermal growth factor) drugs. Objectives: There has been very few reports about the frequency of NRAS mutation from Iran and no study from south of the country. In this article we will describe our experience about the frequency of NRAS mutation in colorectal cancers from the largest referral center in the south of Iran. METHODS During 5 years (2011-2015), we had 52 cases of colorectal cancers with wild type KRAS and BRAF in the hospitals affiliated to Shiraz University of Medical Sciences with enough tissue for molecular studies. NRAS mutation analysis was performed on paraffin embedded formalin fixed tissue of these cases by polymerase chain reaction (PCR)-sequencing method. RESULTS Among these 52 cases of colorectal cancer with wild type KRAS and BRAF, there has been 3 (5.7%) cases with mutant NRAS. One of the mutations has been in codon 12 and two in codon 61. No mutation in codon 13 was found. All the three cases were women with stage IV and well differentiated histomorphology. CONCLUSION Our results showed that frequency of NRAS mutation in colorectal cancer is rare, which is very close to other studies from different geographic areas of the world.

Frequency of NRAS gene mutations among the patients with wild type KRAS colorectal cancers in Southern-Eastern Serbia

“…The results of our study are in concordance with previous studies, where NRAS gene mutations were usually observed in codons 12 and 13 (exon 2), codon 61 (exon 3) and codons 117 and 146 (exon 4). Also, similarly to previous studies, where the frequency of these mutations ranged between 0 to 7.4 % (IRAHARA et al, 2010;AL-SHAMSI et al, 2016;MOMENZADEH et al, 2018;CHANG et al, 2016;BANDO et al, 2013;PALOMBA et al, 2016;NASERI et al, 2016;DOUILLARD et al, 2016), we have also noticed that frequency of NRAS gene mutation in patients with CRC is relatively low, i.e., of 55 tested patients in this study, only 3 of them (5.4%) had a mutation in NRAS gene. The results of the study of Prior and associates, 60% of NRAS mutations were found in codon 61 (PRIOR et al, 2012), and our study had similar results.…”

“…Additionally, many studies have shown that mutations in the NRAS gene can lead to low response on anti-EGFR therapy (IRAHARA et al, 2010;WANG et al, 2013;DI BARTOLOMEO et al, 2014;MODEST et al, 2016;AL-SHAMSI et al, 2016). That is why it is of crucial importance to additionally test CRC patients with wt KRAS for the presence of NRAS gene mutation (MOMENZADEH et al, 2018).…”