Determination of Pathogenic Mutations in NT۵C۲ Gene using Bioinformatics Tools

Backgrounds: About ۱۵% to ۲۰% of children suffering acute lymphoblastic leukemia (ALL),experience a relapse, which is an important reason for death in children. Purine nucleotideanalogs are frequently prescribed in the maintenance therapy of ALL. ۵´ nucleotidase II(NT۵C۲) catalyzes the ۵´ dephosphorylation of purine analogs. Gain-of-function mutations in theNT۵C۲ gene result in resistance to the treatment with purine analogs and subsequently relapse inALL patients. These mutations are common in relapsed ALL cases.Materials and Methods: In the present study, we assessed the pathogenicity of single nucleotidepolymorphisms (SNPs) of the NT۵C۲ gene using bioinformatics tools. So, ۳۵۲ missense variantswere retrieved from the NCBI dbSNP database and at the first step analyzed by SIFT,PROVEAN, PMut, and PANTHER. Then, SNPs that were predicted to be deleterious by at leastthree of the mentioned servers were further analyzed using PolyPhen۲, SNPs & Go, and PhDSNPservers.Results: Intronic and synonymous SNPs were ۷۲ and ۵, respectively. ۱۲۱ SNPs were predictedto be functionally damaging by SIFT, PROVEAN, PMut, and PANTHER, while the rest wereneutral. Then, these ۱۲۱ SNPs were further evaluated by PolyPhen۲, SNPs & Go, and PhD-SNPservers. Finally, ۳۶ SNPs were predicted to be disease-related using all seven tools.Conclusion: Recognition of biomarkers is especially significant in the prediction of relapse inthe treatment of ALL patients. Here, we determined ۳۶ high-risk and deleterious SNPs of theNT۵C۲ gene that can be used to predict resistance to chemotherapy and relapse in ALL patients.

کلیدواژه ها:

Relapsed ALL ، SIFT ، PROVEAN ، PolyPhen۲ ، PANTHER