{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:48:05Z","timestamp":1785829685974,"version":"3.56.0"},"reference-count":75,"publisher":"American Association for Cancer Research (AACR)","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":176,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"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","id":[{"id":"10.13039\/100009164","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA256193"],"award-info":[{"award-number":["R01CA256193"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"publisher","award":["RR220010"],"award-info":[{"award-number":["RR220010"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA142543"],"award-info":[{"award-number":["P30CA142543"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30EY030413"],"award-info":[{"award-number":["P30EY030413"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA256193"],"award-info":[{"award-number":["R01CA256193"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA142543"],"award-info":[{"award-number":["P30CA142543"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005190","name":"Melanoma Research Alliance","doi-asserted-by":"publisher","award":["https:\/\/doi.org\/10.48050\/pc.gr.154417"],"award-info":[{"award-number":["https:\/\/doi.org\/10.48050\/pc.gr.154417"]}],"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\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA076292"],"award-info":[{"award-number":["P30CA076292"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA256193"],"award-info":[{"award-number":["R01CA256193"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY030413"],"award-info":[{"award-number":["P30EY030413"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Challenge Grant"],"award-info":[{"award-number":["Challenge Grant"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Uveal melanoma is a highly aggressive intraocular malignancy with limited therapeutic options for metastatic disease. Existing transgenic uveal melanoma mouse models inadequately recapitulate human disease progression, whereas transplant models lack immune competence for studying the tumor immune microenvironment and therapeutic interventions. To address these limitations, we developed a genetically engineered mouse model incorporating stepwise genetic alterations implicated in human uveal melanoma progression. Spatiotemporally controlled expression of mutant GNAQQ209L from the endogenous locus induced choroidal nevi with limited penetrance. Concomitant BAP1 deletion enhanced nevus formation, whereas further MYC activation led to fully penetrant intraocular tumors with the potential to disseminate. Single-cell RNA sequencing revealed that malignant cells segregated into melanocytic and neural crest\u2013like subpopulations characterized by distinct transcriptional and biosynthetic programs. Trajectory analyses inferred dedifferentiation from the melanocytic toward the neural crest\u2013like state during tumor progression. Comparison with human uveal melanoma revealed commonalities with highly aggressive class 2 uveal melanoma, including gene expression signatures and copy-number gains affecting genes that map to human chromosome 8q beyond the activated MYC allele, suggesting cooperative effects of multiple drivers in this chromosomal region. The tumor microenvironment featured immunosuppressive macrophage populations and exhausted T cells, closely resembling human uveal melanoma. This physiologically relevant, immune-competent model provides a platform for investigating uveal melanoma biology, functionally characterizing candidate driver genes, and developing immune-based therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Development of a mouse model resembling the genetic progression and phenotypic plasticity of human uveal melanoma offers an immune-competent preclinical platform for understanding disease immunogenomics and testing immune and targeted treatments.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/0008-5472.can-25-2684","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T16:52:49Z","timestamp":1770655969000},"page":"3666-3686","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Multistep Immune-Competent Genetically Engineered Mouse Model Reveals Phenotypic Plasticity in Uveal Melanoma"],"prefix":"10.1158","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7366-580X","authenticated-orcid":false,"given":"Xiaonan","family":"Xu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6386-1527","authenticated-orcid":false,"given":"Xiaoxian","family":"Liu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 2 Department of Biostatistics and Bioinformatics, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8877-3292","authenticated-orcid":false,"given":"Vinesh","family":"Jarajapu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-3956","authenticated-orcid":false,"given":"Sathya","family":"Neelature Sriramareddy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 3 Department of Tumor Microenvironment and Metastasis, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5930-8040","authenticated-orcid":false,"given":"Filip","family":"Konecny","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 4 Comparative Medicine, , Tampa, Florida."},{"name":"5Division of Plastic Surgery, Department of Surgery, McMaster University, Hamilton, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7022-5547","authenticated-orcid":false,"given":"Benjamin","family":"Posorske","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-4272","authenticated-orcid":false,"given":"James J.","family":"Dollar","sequence":"additional","affiliation":[{"name":"6Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida."},{"name":"7Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida."},{"name":"8Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0654-7333","authenticated-orcid":false,"given":"Xiao","family":"Liu","sequence":"additional","affiliation":[{"name":"9Department of Ophthalmology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-5554","authenticated-orcid":false,"given":"Neel","family":"Jasani","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-7041","authenticated-orcid":false,"given":"Kaizhen","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."},{"name":"10Cancer Biology PhD Program, University of South Florida, Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-5074","authenticated-orcid":false,"given":"Nicol","family":"Mecozzi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."},{"name":"10Cancer Biology PhD Program, University of South Florida, Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3174-4104","authenticated-orcid":false,"given":"Zulaida","family":"Soto-Vargas","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-2355","authenticated-orcid":false,"given":"Shaaron L.","family":"Ochoa-Rios","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5206-7035","authenticated-orcid":false,"given":"Harini","family":"Murikipudi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2168-9278","authenticated-orcid":false,"given":"Nhan","family":"Phan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7050-080X","authenticated-orcid":false,"given":"Manon","family":"Chadourne","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6197-2642","authenticated-orcid":false,"given":"Jeffim N.","family":"Kuznetsoff","sequence":"additional","affiliation":[{"name":"6Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida."},{"name":"7Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida."},{"name":"8Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8739-517X","authenticated-orcid":false,"given":"John","family":"Sinard","sequence":"additional","affiliation":[{"name":"11Department of Pathology, Yale University School of Medicine, New Haven, Connecticut."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0243-2443","authenticated-orcid":false,"given":"Richard L.","family":"Bennett","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Florida 12 Division of Hematology\/Oncology, University of Florida Health Cancer Center, , Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3942-1369","authenticated-orcid":false,"given":"Jonathan D.","family":"Licht","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02y3ad647","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Florida 12 Division of Hematology\/Oncology, University of Florida Health Cancer Center, , Gainesville, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-9307","authenticated-orcid":false,"given":"Keiran S.M.","family":"Smalley","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 3 Department of Tumor Microenvironment and Metastasis, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1104-9809","authenticated-orcid":false,"given":"J. William","family":"Harbour","sequence":"additional","affiliation":[{"name":"9Department of Ophthalmology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4585-9372","authenticated-orcid":false,"given":"Xiaoqing","family":"Yu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 2 Department of Biostatistics and Bioinformatics, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2350-9809","authenticated-orcid":false,"given":"Florian A.","family":"Karreth","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01xf75524","id-type":"ROR","asserted-by":"publisher"}],"name":"H. Lee Moffitt Cancer Center and Research Institute 1 Department of Molecular Oncology, , Tampa, Florida."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"2026080403154619200_bib1","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.ophtha.2011.01.040","article-title":"Uveal melanoma: trends in incidence, treatment, and survival","volume":"118","author":"Singh","year":"2011","journal-title":"Ophthalmology"},{"key":"2026080403154619200_bib2","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1007\/s11912-025-01684-0","article-title":"State-of-the-art in metastatic uveal melanoma treatment: a 2025 update: how to treat metastatic uveal melanoma in 2025","volume":"27","author":"Ziogas","year":"2025","journal-title":"Curr Oncol Rep"},{"key":"2026080403154619200_bib3","doi-asserted-by":"crossref","first-page":"101041","DOI":"10.1016\/j.preteyeres.2022.101041","article-title":"Metastatic uveal melanoma: the final frontier","volume":"90","author":"Rantala","year":"2022","journal-title":"Prog Retin Eye Res"},{"key":"2026080403154619200_bib4","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ophtha.2025.03.019","article-title":"Surveillance for metastasis in low-risk uveal melanoma patients: the need for optimization","volume":"132","author":"Delaney","year":"2025","journal-title":"Ophthalmology"},{"key":"2026080403154619200_bib5","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/nature07586","article-title":"Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi","volume":"457","author":"Van Raamsdonk","year":"2009","journal-title":"Nature"},{"key":"2026080403154619200_bib6","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1001\/jamaophthalmol.2016.0903","article-title":"Driver mutations in uveal melanoma: associations with gene expression profile and patient outcomes","volume":"134","author":"Decatur","year":"2016","journal-title":"JAMA Ophthalmol"},{"key":"2026080403154619200_bib7","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1016\/j.ophtha.2005.06.011","article-title":"Estimating the risk of malignant transformation of a choroidal nevus","volume":"112","author":"Singh","year":"2005","journal-title":"Ophthalmology"},{"key":"2026080403154619200_bib8","doi-asserted-by":"crossref","first-page":"388","DOI":"10.14694\/EdBook_AM.2013.33.388","article-title":"Genomic, prognostic, and cell-signaling advances in uveal melanoma","volume":"33","author":"Harbour","year":"2013","journal-title":"Am Soc Clin Oncol Educ Book"},{"key":"2026080403154619200_bib9","first-page":"1679","article-title":"Detection of c-myc amplification in uveal melanoma by fluorescent in situ hybridization","volume":"42","author":"Parrella","year":"2001","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2026080403154619200_bib10","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1200\/JCO.24.00447","article-title":"15-Gene expression profile and PRAME as integrated prognostic test for uveal melanoma: first report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1)","volume":"42","author":"Harbour","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026080403154619200_bib11","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ccell.2017.07.003","article-title":"Integrative analysis identifies four molecular and clinical subsets in uveal melanoma","volume":"32","author":"Robertson","year":"2017","journal-title":"Cancer Cell"},{"key":"2026080403154619200_bib12","doi-asserted-by":"crossref","first-page":"3384","DOI":"10.1158\/0008-5472.CAN-14-3229","article-title":"Oncogenic G protein GNAQ induces uveal melanoma and intravasation in mice","volume":"75","author":"Huang","year":"2015","journal-title":"Cancer Res"},{"key":"2026080403154619200_bib13","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1016\/j.celrep.2018.01.081","article-title":"GNA11 Q209L mouse model reveals RasGRP3 as an essential signaling node in uveal melanoma","volume":"22","author":"Moore","year":"2018","journal-title":"Cell Rep"},{"key":"2026080403154619200_bib14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/gene.20180","article-title":"Efficient method to generate single-copy transgenic mice by site-specific integration in embryonic stem cells","volume":"44","author":"Beard","year":"2006","journal-title":"Genesis"},{"key":"2026080403154619200_bib15","doi-asserted-by":"crossref","first-page":"102021","DOI":"10.1016\/j.xpro.2022.102021","article-title":"An intrasplenic injection model of pancreatic cancer metastasis to the liver in mice","volume":"4","author":"O\u2019Brien","year":"2023","journal-title":"STAR Protoc"},{"key":"2026080403154619200_bib16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.ccell.2022.03.008","article-title":"Ovarian cancer immunogenicity is governed by a narrow subset of progenitor tissue-resident memory T cells","volume":"40","author":"Anadon","year":"2022","journal-title":"Cancer Cell"},{"key":"2026080403154619200_bib17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2026080403154619200_bib18","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat Biotechnol"},{"key":"2026080403154619200_bib19","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"2026080403154619200_bib20","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026080403154619200_bib21","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","article-title":"Molecular signatures database (MSigDB) 3.0","volume":"27","author":"Liberzon","year":"2011","journal-title":"Bioinformatics"},{"key":"2026080403154619200_bib22","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"2026080403154619200_bib23","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1038\/nmeth.4463","article-title":"SCENIC: single-cell regulatory network inference and clustering","volume":"14","author":"Aibar","year":"2017","journal-title":"Nat Methods"},{"key":"2026080403154619200_bib24","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1126\/science.1254257","article-title":"Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma","volume":"344","author":"Patel","year":"2014","journal-title":"Science"},{"key":"2026080403154619200_bib25","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/s41586-018-0414-6","article-title":"RNA velocity of single cells","volume":"560","author":"La Manno","year":"2018","journal-title":"Nature"},{"key":"2026080403154619200_bib26","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1038\/s41587-020-0591-3","article-title":"Generalizing RNA velocity to transient cell states through dynamical modeling","volume":"38","author":"Bergen","year":"2020","journal-title":"Nat Biotechnol"},{"key":"2026080403154619200_bib27","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/dvg.20205","article-title":"Characterization of melanocyte-specific inducible Cre recombinase transgenic mice","volume":"44","author":"Bosenberg","year":"2006","journal-title":"Genesis"},{"key":"2026080403154619200_bib28","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.cell.2014.09.014","article-title":"CRISPR-Cas9 knockin mice for genome editing and cancer modeling","volume":"159","author":"Platt","year":"2014","journal-title":"Cell"},{"key":"2026080403154619200_bib29","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s41588-019-0440-9","article-title":"The genetic evolution of metastatic uveal melanoma","volume":"51","author":"Shain","year":"2019","journal-title":"Nat Genet"},{"key":"2026080403154619200_bib30","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/pcmr.12433","article-title":"Insights into genetic alterations of liver metastases from uveal melanoma","volume":"29","author":"McCarthy","year":"2016","journal-title":"Pigment Cell Melanoma Res"},{"key":"2026080403154619200_bib31","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ccell.2016.12.005","article-title":"MYC drives progression of small cell lung cancer to a variant neuroendocrine subtype with vulnerability to Aurora kinase inhibition","volume":"31","author":"Mollaoglu","year":"2017","journal-title":"Cancer Cell"},{"key":"2026080403154619200_bib32","doi-asserted-by":"crossref","first-page":"eabf7472","DOI":"10.1126\/sciadv.abf7472","article-title":"Ciliary protein Kif7 regulates Gli and Ezh2 for initiating the neuronal differentiation of enteric neural crest cells during development","volume":"7","author":"Lai","year":"2021","journal-title":"Sci Adv"},{"key":"2026080403154619200_bib33","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.mod.2018.07.010","article-title":"Gli2 is required for the induction and migration of Xenopus laevis neural crest","volume":"154","author":"Cerrizuela","year":"2018","journal-title":"Mech Dev"},{"key":"2026080403154619200_bib34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ydbio.2013.09.006","article-title":"Pax3 synergizes with Gli2 and Zic1 in transactivating the Myf5 epaxial somite enhancer","volume":"383","author":"Himeda","year":"2013","journal-title":"Dev Biol"},{"key":"2026080403154619200_bib35","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1158\/0008-5472.CAN-10-1032","article-title":"Phosphorylation regulates c-Myc\u2019s oncogenic activity in the mammary gland","volume":"71","author":"Wang","year":"2011","journal-title":"Cancer Res"},{"key":"2026080403154619200_bib36","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41389-020-00261-3","article-title":"Altering MYC phosphorylation in the epidermis increases the stem cell population and contributes to the development, progression, and metastasis of squamous cell carcinoma","volume":"9","author":"Wang","year":"2020","journal-title":"Oncogenesis"},{"key":"2026080403154619200_bib37","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/modpathol.2014.140","article-title":"Scoring of MYC protein expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists","volume":"28","author":"Mahmoud","year":"2015","journal-title":"Mod Pathol"},{"key":"2026080403154619200_bib38","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/s41467-019-14256-1","article-title":"Single-cell analysis reveals new evolutionary complexity in uveal melanoma","volume":"11","author":"Durante","year":"2020","journal-title":"Nat Commun"},{"key":"2026080403154619200_bib39","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.ajo.2005.04.024","article-title":"Association between microarray gene expression signature and extravascular matrix patterns in primary uveal melanomas","volume":"140","author":"Onken","year":"2005","journal-title":"Am J Ophthalmol"},{"key":"2026080403154619200_bib40","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1038\/s41418-025-01469-9","article-title":"Chromosomal 3p loss and 8q gain drive vasculogenic mimicry via HIF-2\u03b1 and VE-cadherin activation in uveal melanoma","volume":"32","author":"Delgado-Bellido","year":"2025","journal-title":"Cell Death Differ"},{"key":"2026080403154619200_bib41","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/s41586-022-05242-7","article-title":"A cellular hierarchy in melanoma uncouples growth and metastasis","volume":"610","author":"Karras","year":"2022","journal-title":"Nature"},{"key":"2026080403154619200_bib42","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/978-1-62703-727-3_22","article-title":"A prognostic test to predict the risk of metastasis in uveal melanoma based on a 15-gene expression profile","volume":"1102","author":"Harbour","year":"2014","journal-title":"Methods Mol Biol"},{"key":"2026080403154619200_bib43","doi-asserted-by":"crossref","first-page":"126027","DOI":"10.1016\/j.ijbiomac.2023.126027","article-title":"Intrinsic disorder may drive the interaction of PROS1 and MERTK in uveal melanoma","volume":"250","author":"Djulbegovic","year":"2023","journal-title":"Int J Biol Macromol"},{"key":"2026080403154619200_bib44","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.3390\/cancers14153678","article-title":"BAP1 loss promotes suppressive tumor immune microenvironment via upregulation of PROS1 in class 2 uveal melanomas","volume":"14","author":"Kaler","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2026080403154619200_bib45","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1038\/s41467-025-56634-y","article-title":"Cooperation between the Hippo and MAPK pathway activation drives acquired resistance to TEAD inhibition","volume":"16","author":"Paul","year":"2025","journal-title":"Nat Commun"},{"key":"2026080403154619200_bib46","doi-asserted-by":"crossref","first-page":"4895","DOI":"10.1038\/s41388-025-03632-5","article-title":"FRA1 drives melanoma metastasis through an actionable transcriptional network","volume":"44","author":"Xu","year":"2025","journal-title":"Oncogene"},{"key":"2026080403154619200_bib47","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41572-020-0158-0","article-title":"Uveal melanoma","volume":"6","author":"Jager","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2026080403154619200_bib48","doi-asserted-by":"crossref","first-page":"100800","DOI":"10.1016\/j.preteyeres.2019.100800","article-title":"Uveal melanoma: towards a molecular understanding","volume":"75","author":"Smit","year":"2020","journal-title":"Prog Retin Eye Res"},{"key":"2026080403154619200_bib49","doi-asserted-by":"crossref","first-page":"19235","DOI":"10.1038\/s41598-019-55513-z","article-title":"Multi-platform omics analysis for identification of molecular characteristics and therapeutic targets of uveal melanoma","volume":"9","author":"Kim","year":"2019","journal-title":"Sci Rep"},{"key":"2026080403154619200_bib50","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.trecan.2022.02.006","article-title":"C1q+ macrophages: passengers or drivers of cancer progression","volume":"8","author":"Revel","year":"2022","journal-title":"Trends Cancer"},{"key":"2026080403154619200_bib51","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1186\/s12967-024-05421-2","article-title":"Single-cell hdWGCNA reveals metastatic protective macrophages and development of deep learning model in uveal melanoma","volume":"22","author":"Sun","year":"2024","journal-title":"J Transl Med"},{"key":"2026080403154619200_bib52","doi-asserted-by":"crossref","first-page":"e007441","DOI":"10.1136\/jitc-2023-007441","article-title":"C1q+ tumor-associated macrophages contribute to immunosuppression through fatty acid metabolic reprogramming in malignant pleural effusion","volume":"11","author":"Zhang","year":"2023","journal-title":"J Immunother Cancer"},{"key":"2026080403154619200_bib53","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1002\/path.5384","article-title":"Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development","volume":"250","author":"Figueiredo","year":"2020","journal-title":"J Pathol"},{"key":"2026080403154619200_bib54","doi-asserted-by":"crossref","first-page":"1161960","DOI":"10.3389\/fimmu.2023.1161960","article-title":"Monoacylglycerol lipase regulates macrophage polarization and cancer progression in uveal melanoma and pan-cancer","volume":"14","author":"Tan","year":"2023","journal-title":"Front Immunol"},{"key":"2026080403154619200_bib55","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41568-019-0154-4","article-title":"Phenotype plasticity as enabler of melanoma progression and therapy resistance","volume":"19","author":"Arozarena","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"2026080403154619200_bib56","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cell.2012.03.003","article-title":"MYC on the path to cancer","volume":"149","author":"Dang","year":"2012","journal-title":"Cell"},{"key":"2026080403154619200_bib57","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1136\/bjo.83.1.110","article-title":"c-myc, p53, and Bcl-2 expression and clinical outcome in uveal melanoma","volume":"83","author":"Chana","year":"1999","journal-title":"Br J Ophthalmol"},{"key":"2026080403154619200_bib58","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41586-025-09503-z","article-title":"Basal cell of origin resolves neuroendocrine-tuft lineage plasticity in cancer","volume":"647","author":"Ireland","year":"2025","journal-title":"Nature"},{"key":"2026080403154619200_bib59","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.ccell.2024.05.003","article-title":"Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer","volume":"42","author":"Finlay","year":"2024","journal-title":"Cancer Cell"},{"key":"2026080403154619200_bib60","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.ccell.2020.05.001","article-title":"MYC drives temporal evolution of small cell lung cancer subtypes by reprogramming neuroendocrine fate","volume":"38","author":"Ireland","year":"2020","journal-title":"Cancer Cell"},{"key":"2026080403154619200_bib61","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.molcel.2012.10.018","article-title":"A genome-wide RNAi screen reveals a trio-regulated Rho GTPase circuitry transducing mitogenic signals initiated by G protein-coupled receptors","volume":"49","author":"Vaqu\u00e9","year":"2013","journal-title":"Mol Cell"},{"key":"2026080403154619200_bib62","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ccr.2014.04.016","article-title":"Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry","volume":"25","author":"Feng","year":"2014","journal-title":"Cancer Cell"},{"key":"2026080403154619200_bib63","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1016\/j.celrep.2019.03.021","article-title":"YAP\/TAZ activation drives uveal melanoma initiation and progression","volume":"29","author":"Li","year":"2019","journal-title":"Cell Rep"},{"key":"2026080403154619200_bib64","doi-asserted-by":"crossref","first-page":"e141797","DOI":"10.1172\/JCI141797","article-title":"SIRP\u03b3-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling","volume":"132","author":"Xu","year":"2022","journal-title":"J Clin Invest"},{"key":"2026080403154619200_bib65","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41419-019-1956-8","article-title":"Dedifferentiation process driven by radiotherapy-induced HMGB1\/TLR2\/YAP\/HIF-1\u03b1 signaling enhances pancreatic cancer stemness","volume":"10","author":"Zhang","year":"2019","journal-title":"Cell Death Dis"},{"key":"2026080403154619200_bib66","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.ophtha.2018.03.011","article-title":"The cancer genome atlas project: an integrated molecular view of uveal melanoma","volume":"125","author":"Jager","year":"2018","journal-title":"Ophthalmology"},{"key":"2026080403154619200_bib67","doi-asserted-by":"crossref","first-page":"5503","DOI":"10.3390\/cancers13215503","article-title":"Genetic landscape and emerging therapies in uveal melanoma","volume":"13","author":"Seedor","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026080403154619200_bib68","doi-asserted-by":"crossref","first-page":"e64370","DOI":"10.7554\/eLife.64370","article-title":"SATB2 induction of a neural crest mesenchyme-like program drives melanoma invasion and drug resistance","volume":"10","author":"Fazio","year":"2021","journal-title":"Elife"},{"key":"2026080403154619200_bib69","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jid.2017.05.038","article-title":"MSX1-induced neural crest-like reprogramming promotes melanoma progression","volume":"138","author":"Heppt","year":"2018","journal-title":"J Invest Dermatol"},{"key":"2026080403154619200_bib70","doi-asserted-by":"crossref","first-page":"5230","DOI":"10.1158\/0008-5472.CAN-20-1496","article-title":"Neural crest-like stem cell transcriptome analysis identifies LPAR1 in melanoma progression and therapy resistance","volume":"81","author":"Liu","year":"2021","journal-title":"Cancer Res"},{"key":"2026080403154619200_bib71","doi-asserted-by":"crossref","first-page":"E131","DOI":"10.1038\/ncb0502-e131","article-title":"AP-1 as a regulator of cell life and death","volume":"4","author":"Shaulian","year":"2002","journal-title":"Nat Cell Biol"},{"key":"2026080403154619200_bib72","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.cell.2010.04.020","article-title":"A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth","volume":"141","author":"Roesch","year":"2010","journal-title":"Cell"},{"key":"2026080403154619200_bib73","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1038\/onc.2016.426","article-title":"FOXO3 is essential for CD44 expression in pancreatic cancer cells","volume":"36","author":"Kumazoe","year":"2017","journal-title":"Oncogene"},{"key":"2026080403154619200_bib74","doi-asserted-by":"crossref","first-page":"e20232094","DOI":"10.1084\/jem.20232094","article-title":"Divergent local and systemic antitumor response in primary uveal melanomas","volume":"221","author":"Lucibello","year":"2024","journal-title":"J Exp Med"},{"key":"2026080403154619200_bib75","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41388-023-02887-0","article-title":"PRAME induces genomic instability in uveal melanoma","volume":"43","author":"Kurtenbach","year":"2024","journal-title":"Oncogene"}],"container-title":["Cancer Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerres\/article-pdf\/doi\/10.1158\/0008-5472.CAN-25-2684\/3736451\/can-25-2684.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article-pdf\/doi\/10.1158\/0008-5472.CAN-25-2684\/3794160\/can-25-2684.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article-pdf\/86\/15\/3666\/3814399\/can-25-2684.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerres\/article-pdf\/86\/15\/3666\/3814399\/can-25-2684.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:16:08Z","timestamp":1785827768000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerres\/article\/86\/15\/3666\/786977\/A-Multistep-Immune-Competent-Genetically"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,9]]},"references-count":75,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,2,9]]},"published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1158\/0008-5472.can-25-2684","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/0008-5472.33151415","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/0008-5472.33151403","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/0008-5472.33151412","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/0008-5472.33151418","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/0008-5472.33151406","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/0008-5472.33151409","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/0008-5472.33151400","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/0008-5472.c.8633048","asserted-by":"object"}]},"ISSN":["0008-5472","1538-7445"],"issn-type":[{"value":"0008-5472","type":"print"},{"value":"1538-7445","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,9]]}}}