Abstract
RAS genes encode highly similar proteins (H-RAS, N-RAS, and K-RAS) of 21-kDa monomers that comprise the largest group of GTPase enzymes. The role of these encoded proteins, particularly the wild type, is as on-and-off molecular switches among active GTP-bound and inactive GDP-bound states. In their active state, RAS proteins turn on genes involved in cell growth and survival. Mutations in RAS coding genes impair GTP hydrolysis activity, leading to the production of persistently active and GTP-bound RAS proteins. Three main missense substitution point mutations at codons 12, 13, and 61 account for the majority of RAS oncogenic transformational status. RAS mutations are associated with approximately 33% of human malignancies. In this study, we aimed to analyze K-RAS and N-RAS oncogene mutations in Saudi leukemia patients in the Tabuk region. A total of 62 samples of peripheral blood from leukemia malignancy patients and 100 samples from healthy controls were enrolled in this study. PCR was performed and sequenced for exons 2 and 3 to detect the three canonical mutations at codons 12, 13, and 61 in the K-RAS and N-RAS oncogenes. For the K-RAS oncogene, we did not find any mutation in either exons 2 or 3 in any leukemia patient or in the healthy controls. For the N-RAS oncogene, we did not find any mutation in exon 2. However, 6 mutations (9.7%) were found in exon 3 for N-RAS samples of leukemia patients compared with the healthy controls and the reference gene in the database. The transition mutation changed the codon GGT to codon CGT, which changed the amino acid Gly to Arg.In our study, we did not find any mutation in all known codons (12, 13 and 61) in leukemia patients. However, a mutation was found in codon number 48, and this could be a novel important mutation in leukemia patients.