Leila Hamzehzadeh1, Fatemeh Khadangi2, Ehsan Ghayoor Karimiani3, Alireza Pasdar4, Mohammad Amin Kerachian5. 1. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran. 3. Razavi Cancer Research Center, Razavi Hospital, Imam Reza International University, Mashhad, Iran; Division of Evolution and Genomic Sciences, Faculty of Biology, Medicine and Health Sciences, University of Manchester, UK. 4. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Division of Applied Medicine, Medical School, University of Aberdeen, Foresterhill, Aberdeen, UK. Electronic address: a.pasdar@abdn.ac.uk. 5. Department of Medical Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Cancer Genetics Research Unit, Reza Radiotherapy and Oncology Center, Mashhad, Iran; Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: amin.kerachian@mail.mcgill.ca.
Abstract
OBJECTIVES: Mutation analysis of the Epidermal Growth Factor Receptor downstream has been a main part of colorectal carcinoma evaluation. Large prospective clinical trials have shown only colorectal cancer (CRC) with wild-type KRAS and NRAS responds to anti-Epidermal Growth Factor Receptor treatment. Hence, mutation analysis is necessary prior to treatment. It is essential to conduct studies to learn about the mutation signature of such tumors. The aim of this study was to evaluate the frequency of hotspot mutations in KRAS and NRAS genes in Iranian CRC patients and to explore their correlations with clinicopathologic parameters. METHODS: We detected mutations in exon 2 (codons 12 and 13) of the KRAS and NRAS genes using high resolution melting analysis, Intplex design and Sanger sequencing in 87 Iranian CRC patients. Genomic DNA was isolated from fresh tissue samples of CRC patients. RESULTS: From 87 eligible cases, 51 were male and 36 were females. KRAS mutations in codons 12 and 13 were present in 28.7% of all analyzed CRCs. Our findings suggested that the tumors with KRAS mutations are not with well- and moderately differentiated tumors compared to poorly differentiated tumors (P value = 0.32). The most frequent types of mutations were glycine to aspartate on codon 12 (p.G12D), and glycine to aspartate on codon 13 (p.G13D). No mutation was found in the NRAS gene in our patients. CONCLUSIONS: Based on this study, the frequency of KRAS mutations seems to be in the spectrum of frequencies of other countries such as China, Japan, India, USA, France, and Germany and NRAS was similar to the West of Iran.
OBJECTIVES: Mutation analysis of the Epidermal Growth Factor Receptor downstream has been a main part of colorectal carcinoma evaluation. Large prospective clinical trials have shown only colorectal cancer (CRC) with wild-type KRAS and NRAS responds to anti-Epidermal Growth Factor Receptor treatment. Hence, mutation analysis is necessary prior to treatment. It is essential to conduct studies to learn about the mutation signature of such tumors. The aim of this study was to evaluate the frequency of hotspot mutations in KRAS and NRAS genes in Iranian CRC patients and to explore their correlations with clinicopathologic parameters. METHODS: We detected mutations in exon 2 (codons 12 and 13) of the KRAS and NRAS genes using high resolution melting analysis, Intplex design and Sanger sequencing in 87 Iranian CRC patients. Genomic DNA was isolated from fresh tissue samples of CRC patients. RESULTS: From 87 eligible cases, 51 were male and 36 were females. KRAS mutations in codons 12 and 13 were present in 28.7% of all analyzed CRCs. Our findings suggested that the tumors with KRAS mutations are not with well- and moderately differentiated tumors compared to poorly differentiated tumors (P value = 0.32). The most frequent types of mutations were glycine to aspartate on codon 12 (p.G12D), and glycine to aspartate on codon 13 (p.G13D). No mutation was found in the NRAS gene in our patients. CONCLUSIONS: Based on this study, the frequency of KRAS mutations seems to be in the spectrum of frequencies of other countries such as China, Japan, India, USA, France, and Germany and NRAS was similar to the West of Iran.
Authors: Hafeez Afolabi; Salzihan Md Salleh; Zaidi Zakaria; Ch'ng Ewe Seng; Siti Norasikin Binti Mohd Nafil; Ahmad Aizat Bin Abdul Aziz; Yusuf Wada; Ahmad Irekeola Journal: Biomed Res Int Date: 2022-06-23 Impact factor: 3.246