{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:50:56Z","timestamp":1791183056600,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1F99CA305524\u201001"],"award-info":[{"award-number":["1F99CA305524\u201001"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"publisher","award":["935329"],"award-info":[{"award-number":["935329"]}],"id":[{"id":"10.13039\/100005190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["ME230182"],"award-info":[{"award-number":["ME230182"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002224","name":"Melanoma Research Foundation","doi-asserted-by":"publisher","award":["1068914"],"award-info":[{"award-number":["1068914"]}],"id":[{"id":"10.13039\/100002224","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009164","name":"Moffitt Cancer Center","doi-asserted-by":"publisher","award":["P30CA076292"],"award-info":[{"award-number":["P30CA076292"]}],"id":[{"id":"10.13039\/100009164","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Uveal melanoma (UM) is driven by activating GNAQ\/GNA11 mutations, predominantly at the hotspot Q209 residue. However, the functional impact of distinct GNAQ Q209 substitutions on downstream signaling and malignant progression remains unclear. Using immune\u2010competent, multistep UM mouse models combining eye\u2010restricted mutant GNAQ with BAP1 loss and MYC activation, we directly compared GNAQ\n                    <jats:sup>Q209L<\/jats:sup>\n                    and GNAQ\n                    <jats:sup>Q209R<\/jats:sup>\n                    in an otherwise matched genetic context. Tumors arising from either allele shared similar histology and cell\u2010state composition. However, GNAQ\n                    <jats:sup>Q209L<\/jats:sup>\n                    tumors progressed faster and were associated with reduced survival. In contrast, GNAQ\n                    <jats:sup>Q209R<\/jats:sup>\n                    tumor\u2010derived cell lines exhibited greater ex\u00a0vivo fitness (proliferation, clonogenicity, and migration), whereas GNAQ\n                    <jats:sup>Q209L<\/jats:sup>\n                    \u2010derived lines were relatively fragile in 2D culture. At the molecular level, GNAQ\n                    <jats:sup>Q209R<\/jats:sup>\n                    tumors preferentially engaged the FAK\u2010YAP axis in primary lesions and derived cell lines. Together, these results support an allele\u2010dependent, context\u2010specific trade\u2010off in which higher output GNAQ\n                    <jats:sup>Q209L<\/jats:sup>\n                    favors rapid in\u00a0vivo expansion, while GNAQ\n                    <jats:sup>Q209R<\/jats:sup>\n                    promotes adaptability, potentially via FAK\u2010YAP signaling, nominating allele\u2010stratified therapeutic opportunities.\n                  <\/jats:p>","DOI":"10.1111\/pcmr.70121","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:52:24Z","timestamp":1791179544000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Allele\u2010Specific\n                    <scp>GNAQ Q209<\/scp>\n                    Mutations Reveal Context\u2010Dependent Oncogenic Programs in Uveal Melanoma"],"prefix":"10.1111","volume":"39","author":[{"given":"Vinesh","family":"Jarajapu","sequence":"first","affiliation":[{"name":"Department of Molecular Oncology H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-3956","authenticated-orcid":false,"given":"Sathya","family":"Neelature Sriramareddy","sequence":"additional","affiliation":[{"name":"Department of Tumor Microenvironment and Metastasis H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-5074","authenticated-orcid":false,"given":"Nicol","family":"Mecozzi","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"},{"name":"Cancer Biology PhD Program University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-7041","authenticated-orcid":false,"given":"Kaizhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"},{"name":"Cancer Biology PhD Program University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2350-9809","authenticated-orcid":false,"given":"Florian A.","family":"Karreth","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-580X","authenticated-orcid":false,"given":"Xiaonan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular Oncology H. Lee Moffitt Cancer Center and Research Institute  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3606"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xjidi.2021.100076"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201019\u20102924"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.6096"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010023\u201000579\u20101"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456\u2010022\u201009841\u2010w"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010020\u20100158\u20100"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2019.100800"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201023\u20101730"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388\u2010025\u201003632\u20105"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201025\u20102684"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.173435.111"}],"container-title":["Pigment Cell &amp; Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.70121","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/pcmr.70121","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.70121","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.70121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:52:25Z","timestamp":1791179545000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.70121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,4]]},"references-count":12,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1111\/pcmr.70121"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.70121","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,4]]},"assertion":[{"value":"2026-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70121"}}