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 |
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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. |
doi_str_mv | 10.1016/j.gene.2021.146099 |
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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. 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.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2021.146099</identifier><identifier>PMID: 34906645</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>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</subject><ispartof>Gene, 2022-02, Vol.812, p.146099-146099, Article 146099</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-10b6ee04ba2585bbfb5aa50007a8d740323d732fc214d22425f6544d6980aea3</citedby><cites>FETCH-LOGICAL-c356t-10b6ee04ba2585bbfb5aa50007a8d740323d732fc214d22425f6544d6980aea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0378111921006946$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34906645$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Laskar, Shaheen</creatorcontrib><creatorcontrib>Das, Raima</creatorcontrib><creatorcontrib>Kundu, Sharbadeb</creatorcontrib><creatorcontrib>Saha, Amrita</creatorcontrib><creatorcontrib>Nandi, Nilashis</creatorcontrib><creatorcontrib>Choudhury, Yashmin</creatorcontrib><creatorcontrib>Kumar Ghosh, Sankar</creatorcontrib><title>Whole exome sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India</title><title>Gene</title><addtitle>Gene</addtitle><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.</description><subject>Aberrant splicing</subject><subject>Adult</subject><subject>Amino Acid Substitution</subject><subject>Case-Control Studies</subject><subject>Cell Cycle Proteins - chemistry</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Deleterious STEAP3_Arg290His variant</subject><subject>EBV-mediated NPC pathogenesis</subject><subject>Electrostatic potential</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>India</subject><subject>Jagged-1 Protein - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Models, Molecular</subject><subject>Nasopharyngeal Carcinoma - genetics</subject><subject>Nasopharyngeal Neoplasms - genetics</subject><subject>Nuclear Proteins - genetics</subject><subject>Oxidoreductases - chemistry</subject><subject>Oxidoreductases - genetics</subject><subject>P53 signaling pathway</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protein Conformation</subject><subject>Protein Domains</subject><subject>Protein modeling</subject><subject>Receptor, Transforming Growth Factor-beta Type I - genetics</subject><subject>Whole Exome Sequencing - methods</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u2zAQhIkiReOmfYEeCh5zkct_SUAugdGfAEF6CdAjsRJXNg1JVEjZqV-gz10KTnPsXrgLzAwxHyGfOFtzxs2X_XqLI64FE3zNlWF1_YaseFXWBWOyuiArJsuq4JzXl-R9SnuWR2vxjlxKVTNjlF6RP792oUeKv8OANOHTAcfWj1vqHY6z7zwmOu-QTmFebuhpXOSho8vXifrxGPojurzQSUs6wbx7htNyPkAK0w7iadxi9m0g5uAwAO1iGOhDiDkX0kzvRufhA3nbQZ_w48t7RR6_fX3c_Cjuf36_29zeF63UZi44awwiUw0IXemm6RoNoHOtEipXKiaFdKUUXSu4ckIooTujlXKmrhggyCtyfY6dYshV02wHn1rsexgxHJIVhjPFOdMyS8VZ2saQUsTOTtEPuY7lzC747d4uDOyC357xZ9Pnl_xDM6B7tfzjnQU3ZwHmkkeP0abWZ-TofMR2ti74_-X_BXnal7A</recordid><startdate>20220220</startdate><enddate>20220220</enddate><creator>Laskar, Shaheen</creator><creator>Das, Raima</creator><creator>Kundu, Sharbadeb</creator><creator>Saha, Amrita</creator><creator>Nandi, Nilashis</creator><creator>Choudhury, Yashmin</creator><creator>Kumar Ghosh, Sankar</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20220220</creationdate><title>Whole exome sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India</title><author>Laskar, Shaheen ; Das, Raima ; Kundu, Sharbadeb ; Saha, Amrita ; Nandi, Nilashis ; Choudhury, Yashmin ; Kumar Ghosh, Sankar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-10b6ee04ba2585bbfb5aa50007a8d740323d732fc214d22425f6544d6980aea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Aberrant splicing</topic><topic>Adult</topic><topic>Amino Acid Substitution</topic><topic>Case-Control Studies</topic><topic>Cell Cycle Proteins - chemistry</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Deleterious STEAP3_Arg290His variant</topic><topic>EBV-mediated NPC pathogenesis</topic><topic>Electrostatic potential</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>India</topic><topic>Jagged-1 Protein - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Models, Molecular</topic><topic>Nasopharyngeal Carcinoma - genetics</topic><topic>Nasopharyngeal Neoplasms - genetics</topic><topic>Nuclear Proteins - genetics</topic><topic>Oxidoreductases - chemistry</topic><topic>Oxidoreductases - genetics</topic><topic>P53 signaling pathway</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Protein Conformation</topic><topic>Protein Domains</topic><topic>Protein modeling</topic><topic>Receptor, Transforming Growth Factor-beta Type I - genetics</topic><topic>Whole Exome Sequencing - methods</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Laskar, Shaheen</creatorcontrib><creatorcontrib>Das, Raima</creatorcontrib><creatorcontrib>Kundu, Sharbadeb</creatorcontrib><creatorcontrib>Saha, Amrita</creatorcontrib><creatorcontrib>Nandi, Nilashis</creatorcontrib><creatorcontrib>Choudhury, Yashmin</creatorcontrib><creatorcontrib>Kumar Ghosh, Sankar</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Laskar, Shaheen</au><au>Das, Raima</au><au>Kundu, Sharbadeb</au><au>Saha, Amrita</au><au>Nandi, Nilashis</au><au>Choudhury, Yashmin</au><au>Kumar Ghosh, Sankar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Whole exome sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2022-02-20</date><risdate>2022</risdate><volume>812</volume><spage>146099</spage><epage>146099</epage><pages>146099-146099</pages><artnum>146099</artnum><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>•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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34906645</pmid><doi>10.1016/j.gene.2021.146099</doi><tpages>1</tpages></addata></record> |
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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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