Iranian journal of Pediatric Hematology and Oncology
Iranian journal of Pediatric Hematology and Oncology
Iran J Ped Hematol Oncol
Medical Sciences
http://ijpho.ssu.ac.ir
1
admin
2008-8892
2228-6993
8
7
14
8888
13
en
jalali
1401
7
1
gregorian
2022
10
1
12
4
online
1
fulltext
en
A comprehensive in silico analysis of pathogenic nsSNPs in the NT5C2 gene involved in relapsed ALL
قلب
Heart
پژوهشي
Research
<div style="border:double windowtext 1.5pt; padding:1.0pt 4.0pt 1.0pt 4.0pt"><span style="font-size:11pt"><span style="line-height:normal"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Background: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">About 10-20% of children suffering from acute lymphoblastic leukemia (ALL), experience a relapse, which is a major cause of their death. Purine nucleotide analogs are frequently prescribed to maintain the treatment of ALL. Cytosolic 5´-nucleotidase (NT5C2) catalyzes the 5´ dephosphorylation of purine analogs. Gain-of-function mutations in the <i>NT5C2</i> gene result in resistance to the treatment with purine analogs and subsequently in the relapse of the disease. </span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Materials and Methods: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">In this descriptive study, bioinformatics tools were used to assess the effect of single nucleotide polymorphisms (SNPs) in the <i>NT5C2</i> gene on the function and structure of the protein. So, 352 missense variants were retrieved from the NCBI database and analyzed by SIFT, PROVEAN, PMut, PANTHER, PolyPhen2, SNPs & Go, and PhD-SNP servers. Then, structural evaluations were performed using HOPE, NetSurp-2.0, and PyMOL. Moreover, stability and evolutionary preservation were assessed by I-Mutant2.0 and ConSurf, respectively. </span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Results: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">As many as 31 nsSNPs were predicted to be affecting the protein function and stability. Also, the native residues were found to be evolutionarily preserved. The structural evaluation demonstrated that a change of hydrophobicity, flexibility, size, charge, or surface accessibility due to 24 nsSNPs would lead to the change of noncovalent interactions and then the conformation of the protein. </span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><span sans-serif="" style="font-family:Calibri,"><b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Conclusion: </span></span></b><span style="font-size:10.0pt"><span new="" roman="" style="font-family:" times="">Identification of biomarkers is significant in the prediction of relapses in ALL children. In this study, bioinformatics tools served to identify 24 high-risk deleterious nsSNPs in the <i>NT5C2</i> gene. These mutations can be used to predict resistance to chemotherapy and relapse in ALL patients. </span></span></span></span></span></div>
Bioinformatics tools, NT5C2 gene, 5´-nucleotidase, Pathogenicity prediction, Relapsed ALL
246
262
http://ijpho.ssu.ac.ir/browse.php?a_code=A-10-931-1&slc_lang=en&sid=1
Reyhane
Chamani
chamani@yazd.ac.ir
0000-0002-5160-0159
Yes
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
Parnia Sadat
Pourhesseini MahmoudAbadi
0000-0003-1590-4267
No
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
Yasamin
Janati
0000-0001-7136-7078
No
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
Roxana
Tajdini
0000-0003-3005-909X
No
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran
Department of Biology, Faculty of Science, Yazd University, Yazd, Iran