Whole exome sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India

•p53 pathway harborsthe maximum percentage of clinically deleterious variants.•rs138941861 in STEAP3 gene was the most deleterious exonic unique-case variant.•STEAP3_Arg290His (rs138941861) variant affecting ESP alter functionality of protein.•STEAP3 is probably associated with EBV-mediatedNPC patho...

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Veröffentlicht in:Gene 2022-02, Vol.812, p.146099-146099, Article 146099
Hauptverfasser: Laskar, Shaheen, Das, Raima, Kundu, Sharbadeb, Saha, Amrita, Nandi, Nilashis, Choudhury, Yashmin, Kumar Ghosh, Sankar
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container_start_page 146099
container_title Gene
container_volume 812
creator Laskar, Shaheen
Das, Raima
Kundu, Sharbadeb
Saha, Amrita
Nandi, Nilashis
Choudhury, Yashmin
Kumar Ghosh, Sankar
description •p53 pathway harborsthe maximum percentage of clinically deleterious variants.•rs138941861 in STEAP3 gene was the most deleterious exonic unique-case variant.•STEAP3_Arg290His (rs138941861) variant affecting ESP alter functionality of protein.•STEAP3 is probably associated with EBV-mediatedNPC pathogenesis.•12 non-coding variants showed significant change in splicing site as well as TFBSs. Nasopharyngeal Carcinoma (NPC) found to be dependent on geographical and racial variation and is more prevalent in Northeast (NE) India. WES-based study was conducted in three states (tribes); Nagaland (Naga), Mizoram (Mizo) and Manipur (Manipuri), which provided an overview of germline variants involved inthemajor signaling pathways. Validation and recurrence assessment of WES data confirmed the risk effect of STEAP3_rs138941861 and JAG1_rs2273059, and the protective role of PARP4_rs17080653 and TGFBR1_rs11568778 variants, where STEAP3_rs138941861conferring Arg290His substitution was the only exonic non-synonymous variant and to be located in proximity to the linking region between the transmembrane and oxidoreductasedomainsof STEAP3 protein, andaffectedits structural and functional dynamics by altering the Electrostatic Potential around this connecting region. Moreover, these significantly associated variants having deleterious effect were observed to have interactions in p53 signaling pathway which emphasizes the importance of this pathway in the causation of NPC.
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Nasopharyngeal Carcinoma (NPC) found to be dependent on geographical and racial variation and is more prevalent in Northeast (NE) India. WES-based study was conducted in three states (tribes); Nagaland (Naga), Mizoram (Mizo) and Manipur (Manipuri), which provided an overview of germline variants involved inthemajor signaling pathways. Validation and recurrence assessment of WES data confirmed the risk effect of STEAP3_rs138941861 and JAG1_rs2273059, and the protective role of PARP4_rs17080653 and TGFBR1_rs11568778 variants, where STEAP3_rs138941861conferring Arg290His substitution was the only exonic non-synonymous variant and to be located in proximity to the linking region between the transmembrane and oxidoreductasedomainsof STEAP3 protein, andaffectedits structural and functional dynamics by altering the Electrostatic Potential around this connecting region. 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source MEDLINE; Elsevier ScienceDirect Journals
subjects Aberrant splicing
Adult
Amino Acid Substitution
Case-Control Studies
Cell Cycle Proteins - chemistry
Cell Cycle Proteins - genetics
Deleterious STEAP3_Arg290His variant
EBV-mediated NPC pathogenesis
Electrostatic potential
Female
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
India
Jagged-1 Protein - genetics
Male
Middle Aged
Models, Molecular
Nasopharyngeal Carcinoma - genetics
Nasopharyngeal Neoplasms - genetics
Nuclear Proteins - genetics
Oxidoreductases - chemistry
Oxidoreductases - genetics
P53 signaling pathway
Polymorphism, Single Nucleotide
Protein Conformation
Protein Domains
Protein modeling
Receptor, Transforming Growth Factor-beta Type I - genetics
Whole Exome Sequencing - methods
title Whole exome sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India
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