Mutation Analysis of KRAS and BRAF in Iranian Colorectal Cancer patients: A Novel Variant in Exon 15 of BRAF

Hassani, Bita; Alizadeh, Rasoul; Akouchekian, Mansoureh; Safarnezhad Tameshkel, Fahimeh; Karbalaie Niya, Mohammad Hadi

doi:10.31557/APJCP.2023.24.11.3665

Mutation Analysis of KRAS and BRAF in Iranian Colorectal Cancer patients: A Novel Variant in Exon 15 of BRAF

Document Type : Research Articles

Authors

¹ Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

² Gastrointestinal and Liver Diseases Research Center, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.

³ Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.

10.31557/APJCP.2023.24.11.3665

Abstract

Background: Mitogen-Activated Protein Kinase (MAPK) pathway and its downstream signaling pathways, play an important role in intracellular signaling. Mutations in KRAS (activating mutation) and BRAF proto-oncogenes are identified as key finding of colorectal cancer. The aim of this study was to examine mutation analysis of KRAS and BRAF in Iranian Colorectal cancer patients. Methods: We used fifty archived formalin fixed paraffin-embedded (FFPE) blocks of Iranian colorectal cancer patients. DNA was extracted from FFPE blocks for PCR assay. The quality of PCR products was determined using horizontal electrophoresis. Then, sequencing and analysis of the sequencing results were performed to investigate variation status in the sequences. Results: KRAS exons and BRAF genes exon 15 in 50 CRC patients were analyzed, among the 19 mutant KRAS samples, 18 (36%) patients had a single base substitution (synonymous mutation) in exon 5, p. Arg161Arg (c.483G>A) and 1 (2%) patient in exon 2 (codon 12), p. Gly12Cys (c.34G>T). Also, we observed two mutations p. Val600Glu (c.1799 T>A) and p. Ser616Thr (c.1846T>A) in exon 15 of BRAF gene. Conclusions: We found a novel variant in BRAF gene. The p. Ser616Thr (c.1846T>A) mutation was not previously reported and we conclude that other new mutations can be identified in KRAS and BRAF which may lead to colorectal cancer.

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