In-Silico Analysis of single nucleotide polymorphisms (SNPs) in PTEN gene associated with T-cell acute lymphoblastic leukemia

Backgrounds: T-cell acute lymphoblastic leukemia (T-ALL) causes the development of T cellsin the thymus. T-ALL affects almost ۱۲% to ۱۵% of pediatric ALL cases. The tumor suppressorgene PTEN (phosphatase and tensin homolog), which is localized ۱۰q۲۳, plays a key role in awide variety of cancers. PTEN is considered as a negative regulator of the PI۳K-AKT signalingpathway that often is inactivated due to various mutations. Our purpose is to determine thepathogenicity of rs۱۲۱۹۰۹۲۲۶ and rs۱۲۱۹۰۹۲۳۰ in cancer malignancy, particularly T-ALL.Materials and Methods: In this study, two SNPs from the PTEN gene (rs۱۲۱۹۰۹۲۲۶,rs۱۲۱۹۰۹۲۳۰) have been identified using Entrez Gene on National Center for BiologicalInformation (NCBI) website. The rs۱۲۱۹۰۹۲۲۶ leads to L۷۰P change and in the rs۱۲۱۹۰۹۲۳۰, Lin position ۱۱۲ changes to P. These SNPs have been analyzed by bioinformatics serverspredicting harmful SNPs, including SIFT, I-Mutant ۲.۰, and Polyphen.Results: SIFT server indicated that the rs۱۲۱۹۰۹۲۲۶ affects the protein function with a score of۰.۰۰. It was predicted to be probably damaging with a score of ۱.۰ by the Polyphen-۲. Plus, the IMutantserver showed a large decrease (about -۱.۴۴) in protein stability. The rs۱۲۱۹۰۹۲۳۰affected the protein function with a score of ۰.۰۰ by SIFT, it would probably be damaging with ascore of ۱.۰۰ by the Polyphen-۲. Additionally, the I-Mutant server showed a large decrease(about -۱.۸۲) in protein stability.Conclusion: This study suggested that L۷۰P and L۱۱۲P variants of PTEN would probably bepathogenic and might have a deleterious effect on the protein function.

کلیدواژه ها:

Acute lymphoblastic leukemia ، PTEN ، SIFT ، Polyphen ، I-Mutant