Somatic mutation analysis in melanoma using targeted next generation sequencing
Advanced stage malignant melanoma often responds poorly to therapy with low survival rates. New therapeutic approaches are based upon a growing understanding of the underlying molecular abnormalities. We demonstrate the feasibility of a next generation sequencing (NGS) assay, which targets hotspots...
Gespeichert in:
| Veröffentlicht in: | Experimental and molecular pathology 2017-10, Vol.103 (2), p.172-177 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 177 |
|---|---|
| container_issue | 2 |
| container_start_page | 172 |
| container_title | Experimental and molecular pathology |
| container_volume | 103 |
| creator | Miraflor, Allen P. de Abreu, Francine B. Peterson, Jason D. Turner, Scott A. Amos, Christopher I. Tsongalis, Gregory J. Yan, Shaofeng |
| description | Advanced stage malignant melanoma often responds poorly to therapy with low survival rates. New therapeutic approaches are based upon a growing understanding of the underlying molecular abnormalities. We demonstrate the feasibility of a next generation sequencing (NGS) assay, which targets hotspots in 50 cancer genes, to assess genotypes that may influence therapeutic selection and response. DNA was extracted from formalin fixed paraffin embedded (FFPE) melanoma specimens to create multiplexed libraries which were sequenced. Of the 121 cases, BRAF mutations were present in 48 cases (40%) and NRAS mutations in 24 cases (20%). We identified other gene variants in 20 BRAF-mutated cases. Additional gene variants were also identified in the 57 BRAF wild-type cases. Four patients harbored different gene mutations at metastatic sites as compared to their primary lesions or metastasis from different sites. Concurrent gene variants may provide additional targets for future therapies and may suggest alternative mechanisms of secondary resistance. |
| doi_str_mv | 10.1016/j.yexmp.2017.08.006 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1930931605</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0014480017304215</els_id><sourcerecordid>1930931605</sourcerecordid><originalsourceid>FETCH-LOGICAL-c359t-377e4189a0029baae6ae4a2f5358eeaecb4360b416f0b29f2f31e22e7f6906673</originalsourceid><addsrcrecordid>eNp9kD1PwzAQhi0EoqXwC5BQRpaEs5048cCAKr6kSh2A2XKSS-WqcYqdoPbf45LCyHTL89579xByTSGhQMXdOtnjrt0mDGieQJEAiBMypSBFDDLNTskUgKZxWgBMyIX3awCQQNk5mbCiYCwXckqWb12re1NF7dCH2dlIW73Ze-MjY6MWN9oGIBq8sauo126FPdaRxV0frdCiGzMePwe0VWAuyVmjNx6vjnNGPp4e3-cv8WL5_Dp_WMQVz2Qf8zzHlBZSAzBZao1CY6pZk_GsQNRYlSkXUKZUNFAy2bCGU2QM80ZIECLnM3I77t26LnT7XrXGV7gJ92I3eEUlB8mpgCygfEQr13nvsFFbZ1rt9oqCOphUa_VjUh1MKihUMBlSN8eCoWyx_sv8qgvA_QhgePPLoFO-MkEC1sZh1au6M_8WfAMl9YbT</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1930931605</pqid></control><display><type>article</type><title>Somatic mutation analysis in melanoma using targeted next generation sequencing</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Miraflor, Allen P. ; de Abreu, Francine B. ; Peterson, Jason D. ; Turner, Scott A. ; Amos, Christopher I. ; Tsongalis, Gregory J. ; Yan, Shaofeng</creator><creatorcontrib>Miraflor, Allen P. ; de Abreu, Francine B. ; Peterson, Jason D. ; Turner, Scott A. ; Amos, Christopher I. ; Tsongalis, Gregory J. ; Yan, Shaofeng</creatorcontrib><description>Advanced stage malignant melanoma often responds poorly to therapy with low survival rates. New therapeutic approaches are based upon a growing understanding of the underlying molecular abnormalities. We demonstrate the feasibility of a next generation sequencing (NGS) assay, which targets hotspots in 50 cancer genes, to assess genotypes that may influence therapeutic selection and response. DNA was extracted from formalin fixed paraffin embedded (FFPE) melanoma specimens to create multiplexed libraries which were sequenced. Of the 121 cases, BRAF mutations were present in 48 cases (40%) and NRAS mutations in 24 cases (20%). We identified other gene variants in 20 BRAF-mutated cases. Additional gene variants were also identified in the 57 BRAF wild-type cases. Four patients harbored different gene mutations at metastatic sites as compared to their primary lesions or metastasis from different sites. Concurrent gene variants may provide additional targets for future therapies and may suggest alternative mechanisms of secondary resistance.</description><identifier>ISSN: 0014-4800</identifier><identifier>EISSN: 1096-0945</identifier><identifier>DOI: 10.1016/j.yexmp.2017.08.006</identifier><identifier>PMID: 28822769</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Biomarkers, Tumor - genetics ; BRA ; DNA Mutational Analysis - methods ; Female ; Genotype ; GTP Phosphohydrolases - genetics ; High-Throughput Nucleotide Sequencing - methods ; Humans ; Male ; Melanoma ; Melanoma - diagnosis ; Melanoma - genetics ; Membrane Proteins - genetics ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Next generation sequencing (NGS) ; NRAS ; Paraffin Embedding ; Prognosis ; Proto-Oncogene Proteins B-raf - genetics ; Retrospective Studies ; Variant</subject><ispartof>Experimental and molecular pathology, 2017-10, Vol.103 (2), p.172-177</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c359t-377e4189a0029baae6ae4a2f5358eeaecb4360b416f0b29f2f31e22e7f6906673</citedby><cites>FETCH-LOGICAL-c359t-377e4189a0029baae6ae4a2f5358eeaecb4360b416f0b29f2f31e22e7f6906673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014480017304215$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28822769$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miraflor, Allen P.</creatorcontrib><creatorcontrib>de Abreu, Francine B.</creatorcontrib><creatorcontrib>Peterson, Jason D.</creatorcontrib><creatorcontrib>Turner, Scott A.</creatorcontrib><creatorcontrib>Amos, Christopher I.</creatorcontrib><creatorcontrib>Tsongalis, Gregory J.</creatorcontrib><creatorcontrib>Yan, Shaofeng</creatorcontrib><title>Somatic mutation analysis in melanoma using targeted next generation sequencing</title><title>Experimental and molecular pathology</title><addtitle>Exp Mol Pathol</addtitle><description>Advanced stage malignant melanoma often responds poorly to therapy with low survival rates. New therapeutic approaches are based upon a growing understanding of the underlying molecular abnormalities. We demonstrate the feasibility of a next generation sequencing (NGS) assay, which targets hotspots in 50 cancer genes, to assess genotypes that may influence therapeutic selection and response. DNA was extracted from formalin fixed paraffin embedded (FFPE) melanoma specimens to create multiplexed libraries which were sequenced. Of the 121 cases, BRAF mutations were present in 48 cases (40%) and NRAS mutations in 24 cases (20%). We identified other gene variants in 20 BRAF-mutated cases. Additional gene variants were also identified in the 57 BRAF wild-type cases. Four patients harbored different gene mutations at metastatic sites as compared to their primary lesions or metastasis from different sites. Concurrent gene variants may provide additional targets for future therapies and may suggest alternative mechanisms of secondary resistance.</description><subject>Biomarkers, Tumor - genetics</subject><subject>BRA</subject><subject>DNA Mutational Analysis - methods</subject><subject>Female</subject><subject>Genotype</subject><subject>GTP Phosphohydrolases - genetics</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Humans</subject><subject>Male</subject><subject>Melanoma</subject><subject>Melanoma - diagnosis</subject><subject>Melanoma - genetics</subject><subject>Membrane Proteins - genetics</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Metastasis</subject><subject>Next generation sequencing (NGS)</subject><subject>NRAS</subject><subject>Paraffin Embedding</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Retrospective Studies</subject><subject>Variant</subject><issn>0014-4800</issn><issn>1096-0945</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD1PwzAQhi0EoqXwC5BQRpaEs5048cCAKr6kSh2A2XKSS-WqcYqdoPbf45LCyHTL89579xByTSGhQMXdOtnjrt0mDGieQJEAiBMypSBFDDLNTskUgKZxWgBMyIX3awCQQNk5mbCiYCwXckqWb12re1NF7dCH2dlIW73Ze-MjY6MWN9oGIBq8sauo126FPdaRxV0frdCiGzMePwe0VWAuyVmjNx6vjnNGPp4e3-cv8WL5_Dp_WMQVz2Qf8zzHlBZSAzBZao1CY6pZk_GsQNRYlSkXUKZUNFAy2bCGU2QM80ZIECLnM3I77t26LnT7XrXGV7gJ92I3eEUlB8mpgCygfEQr13nvsFFbZ1rt9oqCOphUa_VjUh1MKihUMBlSN8eCoWyx_sv8qgvA_QhgePPLoFO-MkEC1sZh1au6M_8WfAMl9YbT</recordid><startdate>201710</startdate><enddate>201710</enddate><creator>Miraflor, Allen P.</creator><creator>de Abreu, Francine B.</creator><creator>Peterson, Jason D.</creator><creator>Turner, Scott A.</creator><creator>Amos, Christopher I.</creator><creator>Tsongalis, Gregory J.</creator><creator>Yan, Shaofeng</creator><general>Elsevier Inc</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>201710</creationdate><title>Somatic mutation analysis in melanoma using targeted next generation sequencing</title><author>Miraflor, Allen P. ; de Abreu, Francine B. ; Peterson, Jason D. ; Turner, Scott A. ; Amos, Christopher I. ; Tsongalis, Gregory J. ; Yan, Shaofeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c359t-377e4189a0029baae6ae4a2f5358eeaecb4360b416f0b29f2f31e22e7f6906673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Biomarkers, Tumor - genetics</topic><topic>BRA</topic><topic>DNA Mutational Analysis - methods</topic><topic>Female</topic><topic>Genotype</topic><topic>GTP Phosphohydrolases - genetics</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>Humans</topic><topic>Male</topic><topic>Melanoma</topic><topic>Melanoma - diagnosis</topic><topic>Melanoma - genetics</topic><topic>Membrane Proteins - genetics</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Next generation sequencing (NGS)</topic><topic>NRAS</topic><topic>Paraffin Embedding</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Retrospective Studies</topic><topic>Variant</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miraflor, Allen P.</creatorcontrib><creatorcontrib>de Abreu, Francine B.</creatorcontrib><creatorcontrib>Peterson, Jason D.</creatorcontrib><creatorcontrib>Turner, Scott A.</creatorcontrib><creatorcontrib>Amos, Christopher I.</creatorcontrib><creatorcontrib>Tsongalis, Gregory J.</creatorcontrib><creatorcontrib>Yan, Shaofeng</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>Experimental and molecular pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miraflor, Allen P.</au><au>de Abreu, Francine B.</au><au>Peterson, Jason D.</au><au>Turner, Scott A.</au><au>Amos, Christopher I.</au><au>Tsongalis, Gregory J.</au><au>Yan, Shaofeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Somatic mutation analysis in melanoma using targeted next generation sequencing</atitle><jtitle>Experimental and molecular pathology</jtitle><addtitle>Exp Mol Pathol</addtitle><date>2017-10</date><risdate>2017</risdate><volume>103</volume><issue>2</issue><spage>172</spage><epage>177</epage><pages>172-177</pages><issn>0014-4800</issn><eissn>1096-0945</eissn><abstract>Advanced stage malignant melanoma often responds poorly to therapy with low survival rates. New therapeutic approaches are based upon a growing understanding of the underlying molecular abnormalities. We demonstrate the feasibility of a next generation sequencing (NGS) assay, which targets hotspots in 50 cancer genes, to assess genotypes that may influence therapeutic selection and response. DNA was extracted from formalin fixed paraffin embedded (FFPE) melanoma specimens to create multiplexed libraries which were sequenced. Of the 121 cases, BRAF mutations were present in 48 cases (40%) and NRAS mutations in 24 cases (20%). We identified other gene variants in 20 BRAF-mutated cases. Additional gene variants were also identified in the 57 BRAF wild-type cases. Four patients harbored different gene mutations at metastatic sites as compared to their primary lesions or metastasis from different sites. Concurrent gene variants may provide additional targets for future therapies and may suggest alternative mechanisms of secondary resistance.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>28822769</pmid><doi>10.1016/j.yexmp.2017.08.006</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0014-4800 |
| ispartof | Experimental and molecular pathology, 2017-10, Vol.103 (2), p.172-177 |
| issn | 0014-4800 1096-0945 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1930931605 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Biomarkers, Tumor - genetics BRA DNA Mutational Analysis - methods Female Genotype GTP Phosphohydrolases - genetics High-Throughput Nucleotide Sequencing - methods Humans Male Melanoma Melanoma - diagnosis Melanoma - genetics Membrane Proteins - genetics Middle Aged Mutation Neoplasm Metastasis Next generation sequencing (NGS) NRAS Paraffin Embedding Prognosis Proto-Oncogene Proteins B-raf - genetics Retrospective Studies Variant |
| title | Somatic mutation analysis in melanoma using targeted next generation sequencing |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T09%3A13%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Somatic%20mutation%20analysis%20in%20melanoma%20using%20targeted%20next%20generation%20sequencing&rft.jtitle=Experimental%20and%20molecular%20pathology&rft.au=Miraflor,%20Allen%20P.&rft.date=2017-10&rft.volume=103&rft.issue=2&rft.spage=172&rft.epage=177&rft.pages=172-177&rft.issn=0014-4800&rft.eissn=1096-0945&rft_id=info:doi/10.1016/j.yexmp.2017.08.006&rft_dat=%3Cproquest_cross%3E1930931605%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1930931605&rft_id=info:pmid/28822769&rft_els_id=S0014480017304215&rfr_iscdi=true |