Genomic analysis reveals low tumor mutation burden which may be associated with GNAQ/11 alteration in a series of primary leptomeningeal melanomas
Primary central nervous system melanoma is rare and characterized by a variable prognosis, and no current treatment guidelines exist. We describe the clinical course of a 70‐year‐old female patient diagnosed with primary leptomeningeal melanoma (LMN) whose case represents the diagnostic and manageme...
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| Veröffentlicht in: | Pigment cell and melanoma research 2020-05, Vol.33 (3), p.458-465 |
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| creator | Fortin Ensign, Shannon Bollin, Kathryn Millis, Sherri Z. Hinds, Brian R. Kosty, Michael Uchiyama, Christopher |
| description | Primary central nervous system melanoma is rare and characterized by a variable prognosis, and no current treatment guidelines exist. We describe the clinical course of a 70‐year‐old female patient diagnosed with primary leptomeningeal melanoma (LMN) whose case represents the diagnostic and management challenges of this tumor. Targeted genomic sequencing of 315 genes from this tumor revealed GNAQ Q209L mutation and low (4 mutations/Megabase) tumor mutation burden (TMB). Wild‐type NRAS, KIT, and BRAF were also observed. A cohort of 4,787 melanomas was subsequently analyzed to identify additional primary central nervous system melanomas, of which 10 additional tumors met pathologic criteria (0.21% of total melanoma cohort). These tumors were genomically assessed according to the same targeted sequencing panel, and 6 of the tumors were also found to harbor a GNAQ mutation. All 10 tumors had low (less than or equal to 2 mutations/Megabase) TMB indicating a potential trend between G‐protein‐coupled receptor (GPCR) alterations and low TMB in LMNs. GPCR alterations were found to significantly correlate with TMB across the cohort of 4,787 melanomas, supporting this potential finding in the limited LMN subset. |
| doi_str_mv | 10.1111/pcmr.12839 |
| format | Article |
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We describe the clinical course of a 70‐year‐old female patient diagnosed with primary leptomeningeal melanoma (LMN) whose case represents the diagnostic and management challenges of this tumor. Targeted genomic sequencing of 315 genes from this tumor revealed GNAQ Q209L mutation and low (4 mutations/Megabase) tumor mutation burden (TMB). Wild‐type NRAS, KIT, and BRAF were also observed. A cohort of 4,787 melanomas was subsequently analyzed to identify additional primary central nervous system melanomas, of which 10 additional tumors met pathologic criteria (0.21% of total melanoma cohort). These tumors were genomically assessed according to the same targeted sequencing panel, and 6 of the tumors were also found to harbor a GNAQ mutation. All 10 tumors had low (less than or equal to 2 mutations/Megabase) TMB indicating a potential trend between G‐protein‐coupled receptor (GPCR) alterations and low TMB in LMNs. GPCR alterations were found to significantly correlate with TMB across the cohort of 4,787 melanomas, supporting this potential finding in the limited LMN subset.</description><identifier>ISSN: 1755-1471</identifier><identifier>EISSN: 1755-148X</identifier><identifier>DOI: 10.1111/pcmr.12839</identifier><identifier>PMID: 31663661</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject>Aged ; Cell Biology ; Central nervous system ; central nervous system/leptomeningeal melanoma ; Cohort Studies ; Dermatology ; Diagnostic systems ; Female ; G protein-coupled receptors ; Gene sequencing ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genomic analysis ; Genomics ; GNAQ/GNA11 ; GTP-Binding Protein alpha Subunits - genetics ; GTP-Binding Protein alpha Subunits, Gq-G11 - genetics ; Humans ; immunotherapy ; Life Sciences & Biomedicine ; Melanoma ; Meningeal Neoplasms - diagnostic imaging ; Meningeal Neoplasms - genetics ; Meninges ; molecular targeted therapy ; Mutation ; Nervous system ; Oncology ; Science & Technology ; Tomography, X-Ray Computed ; tumor mutation burden ; Tumors</subject><ispartof>Pigment cell and melanoma research, 2020-05, Vol.33 (3), p.458-465</ispartof><rights>2019 John Wiley & Sons A/S. 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Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2020 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>2</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000503187400001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c3579-b9b759ba37423251019b4d4bb82c239f9f82b95e1843074b644cde4e5d88f4813</citedby><cites>FETCH-LOGICAL-c3579-b9b759ba37423251019b4d4bb82c239f9f82b95e1843074b644cde4e5d88f4813</cites><orcidid>0000-0002-7433-528X ; 0000-0002-5875-8522</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fpcmr.12839$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fpcmr.12839$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,28253,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31663661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fortin Ensign, Shannon</creatorcontrib><creatorcontrib>Bollin, Kathryn</creatorcontrib><creatorcontrib>Millis, Sherri Z.</creatorcontrib><creatorcontrib>Hinds, Brian R.</creatorcontrib><creatorcontrib>Kosty, Michael</creatorcontrib><creatorcontrib>Uchiyama, Christopher</creatorcontrib><title>Genomic analysis reveals low tumor mutation burden which may be associated with GNAQ/11 alteration in a series of primary leptomeningeal melanomas</title><title>Pigment cell and melanoma research</title><addtitle>PIGM CELL MELANOMA R</addtitle><addtitle>Pigment Cell Melanoma Res</addtitle><description>Primary central nervous system melanoma is rare and characterized by a variable prognosis, and no current treatment guidelines exist. We describe the clinical course of a 70‐year‐old female patient diagnosed with primary leptomeningeal melanoma (LMN) whose case represents the diagnostic and management challenges of this tumor. Targeted genomic sequencing of 315 genes from this tumor revealed GNAQ Q209L mutation and low (4 mutations/Megabase) tumor mutation burden (TMB). Wild‐type NRAS, KIT, and BRAF were also observed. A cohort of 4,787 melanomas was subsequently analyzed to identify additional primary central nervous system melanomas, of which 10 additional tumors met pathologic criteria (0.21% of total melanoma cohort). These tumors were genomically assessed according to the same targeted sequencing panel, and 6 of the tumors were also found to harbor a GNAQ mutation. All 10 tumors had low (less than or equal to 2 mutations/Megabase) TMB indicating a potential trend between G‐protein‐coupled receptor (GPCR) alterations and low TMB in LMNs. GPCR alterations were found to significantly correlate with TMB across the cohort of 4,787 melanomas, supporting this potential finding in the limited LMN subset.</description><subject>Aged</subject><subject>Cell Biology</subject><subject>Central nervous system</subject><subject>central nervous system/leptomeningeal melanoma</subject><subject>Cohort Studies</subject><subject>Dermatology</subject><subject>Diagnostic systems</subject><subject>Female</subject><subject>G protein-coupled receptors</subject><subject>Gene sequencing</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genomic analysis</subject><subject>Genomics</subject><subject>GNAQ/GNA11</subject><subject>GTP-Binding Protein alpha Subunits - genetics</subject><subject>GTP-Binding Protein alpha Subunits, Gq-G11 - genetics</subject><subject>Humans</subject><subject>immunotherapy</subject><subject>Life Sciences & Biomedicine</subject><subject>Melanoma</subject><subject>Meningeal Neoplasms - diagnostic imaging</subject><subject>Meningeal Neoplasms - genetics</subject><subject>Meninges</subject><subject>molecular targeted therapy</subject><subject>Mutation</subject><subject>Nervous system</subject><subject>Oncology</subject><subject>Science & Technology</subject><subject>Tomography, X-Ray Computed</subject><subject>tumor mutation burden</subject><subject>Tumors</subject><issn>1755-1471</issn><issn>1755-148X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkcuO1DAQRSMEYoaBDR-ASmKDQD3jVxJ7OYqgQRqeAoldZDsV2qM4buyEVv8GX4ybNL1ggaiNa3Fu1XXdonhMySXNdbW1Pl5SJrm6U5zTuixXVMivd099Tc-KByndElKRUvH7xRmnVcWrip4XP9c4Bu8s6FEP--QSRPyBekgwhB1Msw8R_DzpyYURzBw7HGG3cXYDXu_BIOiUgnV6wg52btrA-t31xytKQQ8TxkXmRtCQMDpMEHrYRud13MOA2yl4HN34LS8Ej4POVnR6WNzrswF8dHwvii-vXn5uXq9u3q_fNNc3K8vLWq2MMnWpjOa1YJyVlFBlRCeMkcwyrnrVS2ZUiVQKTmphKiFshwLLTspeSMovimfL3G0M32dMU-tdsjhkGxjm1DJOST4To1VGn_6F3oY55osdKMUUkzVhmXq-UDaGlCL27fGrLSXtIan2kFT7O6kMPzmOnI3H7oT-iSYDLxZghyb0yTocLZ4wQkhJOJW1yB050PL_6cYtgTZhHqcspUepG3D_D8_th-btp8X9Ly9cv74</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Fortin Ensign, Shannon</creator><creator>Bollin, Kathryn</creator><creator>Millis, Sherri Z.</creator><creator>Hinds, Brian R.</creator><creator>Kosty, Michael</creator><creator>Uchiyama, Christopher</creator><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><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>7QO</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7433-528X</orcidid><orcidid>https://orcid.org/0000-0002-5875-8522</orcidid></search><sort><creationdate>202005</creationdate><title>Genomic analysis reveals low tumor mutation burden which may be associated with GNAQ/11 alteration in a series of primary leptomeningeal melanomas</title><author>Fortin Ensign, Shannon ; Bollin, Kathryn ; Millis, Sherri Z. ; Hinds, Brian R. ; Kosty, Michael ; Uchiyama, Christopher</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3579-b9b759ba37423251019b4d4bb82c239f9f82b95e1843074b644cde4e5d88f4813</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aged</topic><topic>Cell Biology</topic><topic>Central nervous system</topic><topic>central nervous system/leptomeningeal melanoma</topic><topic>Cohort Studies</topic><topic>Dermatology</topic><topic>Diagnostic systems</topic><topic>Female</topic><topic>G protein-coupled receptors</topic><topic>Gene sequencing</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Genomic analysis</topic><topic>Genomics</topic><topic>GNAQ/GNA11</topic><topic>GTP-Binding Protein alpha Subunits - genetics</topic><topic>GTP-Binding Protein alpha Subunits, Gq-G11 - genetics</topic><topic>Humans</topic><topic>immunotherapy</topic><topic>Life Sciences & Biomedicine</topic><topic>Melanoma</topic><topic>Meningeal Neoplasms - diagnostic imaging</topic><topic>Meningeal Neoplasms - genetics</topic><topic>Meninges</topic><topic>molecular targeted therapy</topic><topic>Mutation</topic><topic>Nervous system</topic><topic>Oncology</topic><topic>Science & Technology</topic><topic>Tomography, X-Ray Computed</topic><topic>tumor mutation burden</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fortin Ensign, Shannon</creatorcontrib><creatorcontrib>Bollin, Kathryn</creatorcontrib><creatorcontrib>Millis, Sherri Z.</creatorcontrib><creatorcontrib>Hinds, Brian R.</creatorcontrib><creatorcontrib>Kosty, Michael</creatorcontrib><creatorcontrib>Uchiyama, Christopher</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pigment cell and melanoma research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fortin Ensign, Shannon</au><au>Bollin, Kathryn</au><au>Millis, Sherri Z.</au><au>Hinds, Brian R.</au><au>Kosty, Michael</au><au>Uchiyama, Christopher</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic analysis reveals low tumor mutation burden which may be associated with GNAQ/11 alteration in a series of primary leptomeningeal melanomas</atitle><jtitle>Pigment cell and melanoma research</jtitle><stitle>PIGM CELL MELANOMA R</stitle><addtitle>Pigment Cell Melanoma Res</addtitle><date>2020-05</date><risdate>2020</risdate><volume>33</volume><issue>3</issue><spage>458</spage><epage>465</epage><pages>458-465</pages><issn>1755-1471</issn><eissn>1755-148X</eissn><abstract>Primary central nervous system melanoma is rare and characterized by a variable prognosis, and no current treatment guidelines exist. We describe the clinical course of a 70‐year‐old female patient diagnosed with primary leptomeningeal melanoma (LMN) whose case represents the diagnostic and management challenges of this tumor. Targeted genomic sequencing of 315 genes from this tumor revealed GNAQ Q209L mutation and low (4 mutations/Megabase) tumor mutation burden (TMB). Wild‐type NRAS, KIT, and BRAF were also observed. A cohort of 4,787 melanomas was subsequently analyzed to identify additional primary central nervous system melanomas, of which 10 additional tumors met pathologic criteria (0.21% of total melanoma cohort). These tumors were genomically assessed according to the same targeted sequencing panel, and 6 of the tumors were also found to harbor a GNAQ mutation. All 10 tumors had low (less than or equal to 2 mutations/Megabase) TMB indicating a potential trend between G‐protein‐coupled receptor (GPCR) alterations and low TMB in LMNs. GPCR alterations were found to significantly correlate with TMB across the cohort of 4,787 melanomas, supporting this potential finding in the limited LMN subset.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>31663661</pmid><doi>10.1111/pcmr.12839</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-7433-528X</orcidid><orcidid>https://orcid.org/0000-0002-5875-8522</orcidid></addata></record> |
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| subjects | Aged Cell Biology Central nervous system central nervous system/leptomeningeal melanoma Cohort Studies Dermatology Diagnostic systems Female G protein-coupled receptors Gene sequencing Genetic Association Studies Genetic Predisposition to Disease Genomic analysis Genomics GNAQ/GNA11 GTP-Binding Protein alpha Subunits - genetics GTP-Binding Protein alpha Subunits, Gq-G11 - genetics Humans immunotherapy Life Sciences & Biomedicine Melanoma Meningeal Neoplasms - diagnostic imaging Meningeal Neoplasms - genetics Meninges molecular targeted therapy Mutation Nervous system Oncology Science & Technology Tomography, X-Ray Computed tumor mutation burden Tumors |
| title | Genomic analysis reveals low tumor mutation burden which may be associated with GNAQ/11 alteration in a series of primary leptomeningeal melanomas |
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