{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:20:47Z","timestamp":1788283247731,"version":"build-2803163510"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Br J Cancer"],"published-print":{"date-parts":[[2026,9,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>The aim of this research is to identify germline genetic variants that predispose to uveal melanoma (UM) using data from nine studies involving 5839 individuals with UM (3853 novel) and 349,863 healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Five novel UM genome-wide association studies (GWAS) were performed and included for meta-analysis with four previously published UM GWAS. A fixed-effects inverse-variance weighted (IVW) meta-analysis was performed by combining data from these nine UM case-control cohorts. A follow-up transcriptome-wide association study (TWAS) was conducted to identify candidate target genes at UM risk loci. Genetic correlations with melanoma-related phenotypes were measured to elucidate UM\u2019s genetic architecture.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identify nine linkage disequilibrium (LD)-independent loci (three novel) with an IVW\n                      <jats:italic>P<\/jats:italic>\n                      value of less than 5\u2009\u00d7\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      . TWAS analysis indicates five potential target genes, including\n                      <jats:italic>MOB3B<\/jats:italic>\n                      ,\n                      <jats:italic>RBAK<\/jats:italic>\n                      , and\n                      <jats:italic>MTSS1<\/jats:italic>\n                      , which have established links to multiple cancer types. We note a significant genetic correlation (rg\u2009=\u20090.31,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.01) between UM and cutaneous melanoma (CM), and a non-significant but consistent correlation with naevus count (rg\u2009=\u20090.25,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.08).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This meta-analysis offers new insights into the genetic architecture of UM, highlights potential therapeutic targets, and explores the genetic relationship with CM and skin pigmentation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41416-026-03499-7","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:42:51Z","timestamp":1781613771000},"page":"983-991","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GWAS meta-analysis provides new insights into uveal melanoma risk"],"prefix":"10.1038","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8979-2419","authenticated-orcid":false,"given":"Matthew","family":"D\u2019Mellow","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2702-522X","authenticated-orcid":false,"given":"Jane M.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kari","family":"Hemminki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Cebulla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5727-7463","authenticated-orcid":false,"given":"Aaron B.","family":"Beasley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos E.","family":"Bechrakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia L.","family":"Pritchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin W.","family":"Wadt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-5452","authenticated-orcid":false,"given":"Peter A.","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenha","family":"Mobuchon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Barlow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Beckman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine M.","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil K.","family":"Warrier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Kalirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colette","family":"Mustard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Ingold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9857-4728","authenticated-orcid":false,"given":"Asta","family":"F\u00f6rsti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Isaacs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. J. M. Shanika R.","family":"Jayasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J.","family":"Glasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayle","family":"Williamson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0925-1124","authenticated-orcid":false,"given":"Lindsay A.","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc-Quynh","family":"Le","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Chadha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8613-3570","authenticated-orcid":false,"given":"Elin S.","family":"Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8558-6711","authenticated-orcid":false,"given":"Kevin M.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Connolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"MacGregor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Whiteman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens F.","family":"Kiilgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8100-2272","authenticated-orcid":false,"given":"Marc-Henri","family":"Stern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1464-2069","authenticated-orcid":false,"given":"Sarah E.","family":"Coupland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H.","family":"Abdel-Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zeschnigk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Hayward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4303-8821","authenticated-orcid":false,"given":"Matthew H.","family":"Law","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"3499_CR1","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/eye.2016.275","volume":"31","author":"S Kaliki","year":"2017","unstructured":"Kaliki S, Shields CL. Uveal melanoma: relatively rare but deadly cancer. Eye. 2017;31:241\u201357.","journal-title":"Eye"},{"key":"3499_CR2","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1167\/iovs.64.13.45","volume":"64","author":"M Wu","year":"2023","unstructured":"Wu M, Yavuzyigitoglu S, Brosens E, Ramdas WD, Kili\u00e7 E. Rotterdam Ocular Melanoma Study Group (ROMS). Worldwide incidence of ocular melanoma and correlation with pigmentation-related risk factors. Investig Ophthalmol Vis Sci. 2023;64:45.","journal-title":"Investig Ophthalmol Vis Sci"},{"key":"3499_CR3","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1158\/2159-8290.CD-13-0330","volume":"3","author":"SJ Furney","year":"2013","unstructured":"Furney SJ, Pedersen M, Gentien D, Dumont AG, Rapinat A, Desjardins L, et al. SF3B1 mutations are associated with alternative splicing in uveal melanoma. Cancer Discov. 2013;3:1122\u20139.","journal-title":"Cancer Discov"},{"key":"3499_CR4","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1016\/j.ajhg.2016.09.008","volume":"99","author":"B Royer-Bertrand","year":"2016","unstructured":"Royer-Bertrand B, Torsello M, Rimoldi D, El Zaoui I, Cisarova K, Pescini-Gobert R, et al. Comprehensive genetic landscape of uveal melanoma by whole-genome sequencing. Am J Hum Genet. 2016;99:1190\u20138.","journal-title":"Am J Hum Genet"},{"key":"3499_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16276-8","volume":"11","author":"PA Johansson","year":"2020","unstructured":"Johansson PA, Brooks K, Newell F, Palmer JM, Wilmott JS, Pritchard AL, et al. Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours. Nat Commun. 2020;11:2408.","journal-title":"Nat Commun"},{"key":"3499_CR6","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1111\/ceo.14424","volume":"52","author":"LA McGrath","year":"2024","unstructured":"McGrath LA, Warrier SK, Glasson WJ, D\u2019Mellow MG, Hamilton HR, Palmer JM, et al. Iris melanoma in an Australian cohort. Clin Experiment Ophthalmol. 2024;52:880\u20137.","journal-title":"Clin Experiment Ophthalmol"},{"key":"3499_CR7","doi-asserted-by":"publisher","DOI":"10.1177\/1758834018757175","volume":"10","author":"J Yang","year":"2018","unstructured":"Yang J, Manson DK, Marr BP, Carvajal RD. Treatment of uveal melanoma: where are we now? Ther Adv Med Oncol. 2018;10:1758834018757175.","journal-title":"Ther Adv Med Oncol"},{"key":"3499_CR8","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/eye.2012.242","volume":"27","author":"B Damato","year":"2013","unstructured":"Damato B, Heimann H. Personalized treatment of uveal melanoma. EYE. 2013;27:172\u20139.","journal-title":"EYE"},{"key":"3499_CR9","doi-asserted-by":"publisher","first-page":"93","DOI":"10.4103\/0301-4738.154367","volume":"63","author":"S Kaliki","year":"2015","unstructured":"Kaliki S, Shields CL, Shields JA. Uveal melanoma: estimating prognosis. Indian J Ophthalmol. 2015;63:93\u2013102.","journal-title":"Indian J Ophthalmol"},{"key":"3499_CR10","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1136\/bjophthalmol-2016-309034","volume":"101","author":"RD Carvajal","year":"2017","unstructured":"Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD. Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol. 2017;101:38\u201344.","journal-title":"Br J Ophthalmol"},{"key":"3499_CR11","doi-asserted-by":"publisher","first-page":"3446","DOI":"10.1002\/cncr.28864","volume":"120","author":"M Burotto","year":"2014","unstructured":"Burotto M, Chiou VL, Lee J-M, Kohn EC. The MAPK pathway across different malignancies: a new perspective. Cancer. 2014;120:3446\u201356.","journal-title":"Cancer"},{"key":"3499_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2022.101041","volume":"90","author":"ES Rantala","year":"2022","unstructured":"Rantala ES, Hernberg MM, Piperno-Neumann S, Grossniklaus HE, Kivel\u00e4 TT. Metastatic uveal melanoma: The final frontier. Prog Retin Eye Res. 2022;90:101041.","journal-title":"Prog Retin Eye Res"},{"key":"3499_CR13","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1056\/NEJMoa2103485","volume":"385","author":"P Nathan","year":"2021","unstructured":"Nathan P, Hassel JC, Rutkowski P, Baurain J-F, Butler MO, Schlaak M, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2021;385:1196\u2013206.","journal-title":"N Engl J Med"},{"key":"3499_CR14","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1056\/NEJMoa2304753","volume":"389","author":"JC Hassel","year":"2023","unstructured":"Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain J-F, Schlaak M, Butler MO, et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2023;389:2256\u201366.","journal-title":"N Engl J Med"},{"key":"3499_CR15","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1007\/s40257-024-00872-1","volume":"25","author":"EAT Koch","year":"2024","unstructured":"Koch EAT, Heppt MV, Berking C. The current state of systemic therapy of metastatic uveal melanoma. Am J Clin Dermatol. 2024;25:691\u2013700.","journal-title":"Am J Clin Dermatol"},{"key":"3499_CR16","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1093\/annonc\/mdz176","volume":"30","author":"L Khoja","year":"2019","unstructured":"Khoja L, Atenafu EG, Suciu S, Leyvraz S, Sato T, Marshall E, et al. Meta-analysis in metastatic uveal melanoma to determine progression free and overall survival benchmarks: an international rare cancers initiative (IRCI) ocular melanoma study. Ann Oncol. 2019;30:1370\u201380.","journal-title":"Ann Oncol"},{"key":"3499_CR17","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1126\/science.1194472","volume":"330","author":"JW Harbour","year":"2010","unstructured":"Harbour JW, Onken MD, Roberson EDO, Duan S, Cao L, Worley LA, et al. Frequent mutation of BAP1 in metastasizing uveal melanomas. Science. 2010;330:1410\u20133.","journal-title":"Science"},{"key":"3499_CR18","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1136\/jmedgenet-2011-100156","volume":"48","author":"MH Abdel-Rahman","year":"2011","unstructured":"Abdel-Rahman MH, Pilarski R, Cebulla CM, Massengill JB, Christopher BN, Boru G, et al. Germline BAP1 mutation predisposes to uveal melanoma, lung adenocarcinoma, meningioma, and other cancers. J Med Genet. 2011;48:856\u20139.","journal-title":"J Med Genet"},{"key":"3499_CR19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1383125","volume":"15","author":"J Matull","year":"2024","unstructured":"Matull J, Placke J-M, Lodde G, Zaremba A, Utikal J, Terheyden P, et al. Clinical and genetic characteristics of BAP1-mutated non-uveal and uveal melanoma. Front Immunol. 2024;15:1383125.","journal-title":"Front Immunol"},{"key":"3499_CR20","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1002\/gcc.10286","volume":"38","author":"C Kannengiesser","year":"2003","unstructured":"Kannengiesser C, Avril M-F, Spatz A, Laud K, Lenoir GM, Bressac-de-Paillerets B. CDKN2A as a uveal and cutaneous melanoma susceptibility gene. Genes Chromosomes Cancer. 2003;38:265\u20138.","journal-title":"Genes Chromosomes Cancer"},{"key":"3499_CR21","doi-asserted-by":"publisher","unstructured":"Rodrigues M, Mobuchon L, Houy A, Fi\u00e9vet A, Gardrat S, Barnhill RL, et al. Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors. Nat Commun. 2018;9. https:\/\/doi.org\/10.1038\/s41467-018-04322-5.","DOI":"10.1038\/s41467-018-04322-5"},{"key":"3499_CR22","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1093\/jnci\/djaa047","volume":"113","author":"A-C Derrien","year":"2021","unstructured":"Derrien A-C, Rodrigues M, Eeckhoutte A, Dayot S, Houy A, Mobuchon L, et al. Germline MBD4 mutations and predisposition to uveal melanoma. J Natl Cancer Inst. 2021;113:80\u20137.","journal-title":"J Natl Cancer Inst"},{"key":"3499_CR23","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s00251-019-01108-x","volume":"71","author":"PA Johansson","year":"2019","unstructured":"Johansson PA, Stark A, Palmer JM, Bigby K, Brooks K, Rolfe O, et al. Prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab. Immunogenetics. 2019;71:433\u20136.","journal-title":"Immunogenetics"},{"key":"3499_CR24","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1002\/ijc.10693","volume":"102","author":"RJ Scott","year":"2002","unstructured":"Scott RJ, Vajdic CM, Armstrong BK, Ainsworth CJ, Meldrum CJ, Aitken JF, et al. BRCA2 mutations in a population-based series of patients with ocular melanoma. Int J Cancer. 2002;102:188\u201391.","journal-title":"Int J Cancer"},{"key":"3499_CR25","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1097\/CMR.0000000000000613","volume":"29","author":"PA Johansson","year":"2019","unstructured":"Johansson PA, Nathan V, Bourke LM, Palmer JM, Zhang T, Symmons J, et al. Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma. Melanoma Res. 2019;29:483\u201390.","journal-title":"Melanoma Res"},{"key":"3499_CR26","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.ophtha.2019.11.009","volume":"127","author":"MH Abdel-Rahman","year":"2020","unstructured":"Abdel-Rahman MH, Sample KM, Pilarski R, Walsh T, Grosel T, Kinnamon D, et al. Whole exome sequencing identifies candidate genes associated with hereditary predisposition to uveal melanoma. Ophthalmology. 2020;127:668\u201378.","journal-title":"Ophthalmology"},{"key":"3499_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/srep31191","volume":"6","author":"R Ferguson","year":"2016","unstructured":"Ferguson R, Vogelsang M, Ucisik-Akkaya E, Rai K, Pilarski R, Martinez CN, et al. Genetic markers of pigmentation are novel risk loci for uveal melanoma. Sci Rep. 2016;6:31191.","journal-title":"Sci Rep"},{"key":"3499_CR28","doi-asserted-by":"publisher","unstructured":"Mobuchon L, Battistella A, Bardel C, Scelo G, Renoud A, Houy A, et al. A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus. npj Genom Med. 2017;2. https:\/\/doi.org\/10.1038\/s41525-017-0008-5.","DOI":"10.1038\/s41525-017-0008-5"},{"key":"3499_CR29","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1097\/CMR.0000000000000641","volume":"30","author":"H Thomsen","year":"2020","unstructured":"Thomsen H, Chattopadhyay S, Hoffmann P, N\u00f6then MM, Kalirai H, Coupland SE, et al. Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1. Melanoma Res. 2020;30:166\u201372.","journal-title":"Melanoma Res"},{"key":"3499_CR30","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1093\/jnci\/djab167","volume":"114","author":"L Mobuchon","year":"2022","unstructured":"Mobuchon L, Derrien A-C, Houy A, Verrier T, Pierron G, Cassoux N, et al. Different pigmentation risk loci for high-risk monosomy 3 and low-risk disomy 3 uveal melanomas. J Natl Cancer Inst. 2022;114:302\u20139.","journal-title":"J Natl Cancer Inst"},{"key":"3499_CR31","doi-asserted-by":"crossref","unstructured":"Mies G, Tsao NL, Houy A, Coupland SE, Kalirai H, F\u00f6rsti A, et al. Meta-analysis of uveal melanoma genome-wide association studies identifies novel risk loci and population effect size heterogeneity. HGG Adv. 2025:100465.","DOI":"10.1016\/j.xhgg.2025.100465"},{"key":"3499_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/thg.2025.15","volume":"28","author":"N-Q Le","year":"2025","unstructured":"Le N-Q, Gharahkhani P, MacGregor S. Genetic similarity clustering using the UK Biobank as a reference dataset. Twin Res Hum Genet. 2025;28:1\u20138.","journal-title":"Twin Res Hum Genet"},{"key":"3499_CR33","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203\u20139.","journal-title":"Nature"},{"key":"3499_CR34","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/s41588-021-00870-7","volume":"53","author":"J Mbatchou","year":"2021","unstructured":"Mbatchou J, Barnard L, Backman J, Marcketta A, Kosmicki JA, Ziyatdinov A, et al. Computationally efficient whole-genome regression for quantitative and binary traits. Nat Genet. 2021;53:1097\u2013103.","journal-title":"Nat Genet"},{"key":"3499_CR35","doi-asserted-by":"publisher","first-page":"E19","DOI":"10.1038\/s41586-023-05837-8","volume":"615","author":"MI Kurki","year":"2023","unstructured":"Kurki MI, Karjalainen J, Palta P, Sipil\u00e4 TP, Kristiansson K, Donner KM, et al. Author Correction: FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;615:E19.","journal-title":"Nature"},{"key":"3499_CR36","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/nature05911","volume":"447","author":"Wellcome Trust Case Control Consortium.","year":"2007","unstructured":"Wellcome Trust Case Control Consortium.Genome-wide association study of 14,000 cases of seven common diseases and 3000 shared controls. Nature. 2007;447:661\u201378.","journal-title":"Nature"},{"key":"3499_CR37","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559\u201375.","journal-title":"Am J Hum Genet"},{"key":"3499_CR38","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience. 2015;4:7.","journal-title":"Gigascience"},{"key":"3499_CR39","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1038\/ng.2213","volume":"44","author":"J Yang","year":"2012","unstructured":"Yang J, Ferreira T, Morris AP, Medland SE. Genetic Investigation of ANthropometric Traits (GIANT) Consortium, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat Genet. 2012;44:369\u201375. S1-3.","journal-title":"Nat Genet"},{"key":"3499_CR40","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1126\/science.aaz1776","volume":"369","author":"GTEx Consortium","year":"2020","unstructured":"GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science. 2020;369:1318\u201330.","journal-title":"Science"},{"key":"3499_CR41","doi-asserted-by":"crossref","unstructured":"Zhang T, Choi J, Kovacs MA, Shi J, Xu M, et al. NISC Comparative Sequencing Program. Cell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes. Genome Res. 2018;28:1621\u201335.","DOI":"10.1101\/gr.233304.117"},{"key":"3499_CR42","doi-asserted-by":"publisher","first-page":"e1004383","DOI":"10.1371\/journal.pgen.1004383","volume":"10","author":"C Giambartolomei","year":"2014","unstructured":"Giambartolomei C, Vukcevic D, Schadt EE, Franke L, Hingorani AD, Wallace C, et al. Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet. 2014;10:e1004383.","journal-title":"PLoS Genet"},{"key":"3499_CR43","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1101\/gr.128652.111","volume":"22","author":"M Visser","year":"2012","unstructured":"Visser M, Kayser M, Palstra R-J. HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res. 2012;22:446\u201355.","journal-title":"Genome Res"},{"key":"3499_CR44","doi-asserted-by":"publisher","first-page":"2649","DOI":"10.1093\/hmg\/ddv029","volume":"24","author":"M Visser","year":"2015","unstructured":"Visser M, Palstra R-J, Kayser M. Allele-specific transcriptional regulation of IRF4 in melanocytes is mediated by chromatin looping of the intronic rs12203592 enhancer to the IRF4 promoter. Hum Mol Genet. 2015;24:2649\u201361.","journal-title":"Hum Mol Genet"},{"key":"3499_CR45","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.7150\/ijbs.40834","volume":"16","author":"Y-N Deng","year":"2020","unstructured":"Deng Y-N, Xia Z, Zhang P, Ejaz S, Liang S. Transcription factor RREB1: from target genes towards biological functions. Int J Biol Sci. 2020;16:1463\u201373.","journal-title":"Int J Biol Sci"},{"key":"3499_CR46","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1038\/s41588-021-00913-z","volume":"53","author":"U V\u00f5sa","year":"2021","unstructured":"V\u00f5sa U, Claringbould A, Westra H-J, Bonder MJ, Deelen P, Zeng B, et al. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet. 2021;53:1300\u201310.","journal-title":"Nat Genet"},{"key":"3499_CR47","first-page":"2942","volume":"18","author":"B He","year":"2019","unstructured":"He B, Wang B, Wang H, Zhang C, Wu Y, Fu L, et al. RBAK is upregulated in non-small cell lung cancer and promotes cell migration and invasion. Exp Ther Med. 2019;18:2942\u20138.","journal-title":"Exp Ther Med"},{"key":"3499_CR48","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.tranon.2016.11.006","volume":"10","author":"D Luxen","year":"2017","unstructured":"Luxen D, Gielen GH, Waha A, Isselstein L, M\u00fcller T, Koch P, et al. MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility. Transl Oncol. 2017;10:70\u20139.","journal-title":"Transl Oncol"},{"key":"3499_CR49","doi-asserted-by":"publisher","first-page":"569","DOI":"10.3390\/cells8060569","volume":"8","author":"R Gundogdu","year":"2019","unstructured":"Gundogdu R, Hergovich A. MOB (mps one binder) proteins in the Hippo pathway and cancer. Cells. 2019;8:569.","journal-title":"Cells"},{"key":"3499_CR50","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1093\/jnci\/djy171","volume":"110","author":"S Walpole","year":"2018","unstructured":"Walpole S, Pritchard AL, Cebulla CM, Pilarski R, Stautberg M, Davidorf FH, et al. Comprehensive study of the clinical phenotype of germline BAP1 variant-carrying families worldwide. J Natl Cancer Inst. 2018;110:1328\u201341.","journal-title":"J Natl Cancer Inst"},{"key":"3499_CR51","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1136\/jmedgenet-2020-107098","volume":"58","author":"V Nathan","year":"2021","unstructured":"Nathan V, Palmer JM, Johansson PA, Hamilton HR, Warrier SK, Glasson W, et al. Loss-of-function variants in POT1 predispose to uveal melanoma. J Med Genet. 2021;58:234\u20136.","journal-title":"J Med Genet"},{"key":"3499_CR52","doi-asserted-by":"publisher","first-page":"7212","DOI":"10.1074\/jbc.275.10.7212","volume":"275","author":"SX Skapek","year":"2000","unstructured":"Skapek SX, Jansen D, Wei TF, McDermott T, Huang W, Olson EN, et al. Cloning and characterization of a novel Kruppel-associated box family transcriptional repressor that interacts with the retinoblastoma gene product, RB. J Biol Chem. 2000;275:7212\u201323.","journal-title":"J Biol Chem"},{"key":"3499_CR53","doi-asserted-by":"publisher","unstructured":"V\u00e9lez-Cruz R, Johnson DG. The retinoblastoma (RB) tumor suppressor: pushing back against genome instability on multiple fronts. Int J Mol Sci. 2017;18 https:\/\/doi.org\/10.3390\/ijms18081776.","DOI":"10.3390\/ijms18081776"},{"key":"3499_CR54","doi-asserted-by":"publisher","first-page":"621","DOI":"10.2741\/s175","volume":"S3","author":"F Xie","year":"2011","unstructured":"Xie F. MTSS1 a multifunctional protein and its role in cancer invasion and metastasis. Front Biosci (Schol Ed). 2011;S3:621\u201331.","journal-title":"Front Biosci (Schol Ed)"},{"key":"3499_CR55","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1007\/s00018-024-05511-w","volume":"81","author":"L Matskova","year":"2024","unstructured":"Matskova L, Zheng S, Kashuba E, Ernberg I, Aspenstr\u00f6m P. MTSS1: beyond the integration of actin and membrane dynamics. Cell Mol Life Sci. 2024;81:472.","journal-title":"Cell Mol Life Sci"},{"key":"3499_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4465","volume":"5","author":"KD Mertz","year":"2014","unstructured":"Mertz KD, Pathria G, Wagner C, Saarikangas J, Sboner A, Romanov J, et al. MTSS1 is a metastasis driver in a subset of human melanomas. Nat Commun. 2014;5:3465.","journal-title":"Nat Commun"},{"key":"3499_CR57","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s13046-020-01735-3","volume":"39","author":"C Du","year":"2020","unstructured":"Du C, Lv C, Feng Y, Yu S. Activation of the KDM5A\/miRNA-495\/YTHDF2\/m6A-MOB3B axis facilitates prostate cancer progression. J Exp Clin Cancer Res. 2020;39:223.","journal-title":"J Exp Clin Cancer Res"},{"key":"3499_CR58","doi-asserted-by":"publisher","unstructured":"Winkler PA, Dawson-Baglien EM, Coffey MC, Venta PJ, Ekenstedt KJ, Petersen-Jones SM. Mapping the locus for ocular melanosis in Cairn Terriers. Vet Ophthalmol. 2024 https:\/\/doi.org\/10.1111\/vop.13291.","DOI":"10.1111\/vop.13291"},{"key":"3499_CR59","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1001\/jamaophthalmol.2013.129","volume":"131","author":"CL Shields","year":"2013","unstructured":"Shields CL, Kaliki S, Livesey M, Walker B, Garoon R, Bucci M, et al. Association of ocular and oculodermal melanocytosis with the rate of uveal melanoma metastasis: analysis of 7872 consecutive eyes. JAMA Ophthalmol. 2013;131:993\u20131003.","journal-title":"JAMA Ophthalmol"},{"key":"3499_CR60","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1016\/j.cell.2024.03.011","volume":"187","author":"T Cao","year":"2024","unstructured":"Cao T, Zhang W, Wang Q, Wang C, Ma W, Zhang C, et al. Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8+ T cells. Cell. 2024;187:2288\u2013304.e27.","journal-title":"Cell"},{"key":"3499_CR61","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/j.1440-1746.2010.06434.x","volume":"26","author":"X-T Liang","year":"2011","unstructured":"Liang X-T, Pan K, Chen M-S, Li J-J, Wang H, Zhao J-J, et al. Decreased expression of XPO4 is associated with poor prognosis in hepatocellular carcinoma. J Gastroenterol Hepatol. 2011;26:544\u20139.","journal-title":"J Gastroenterol Hepatol"},{"key":"3499_CR62","doi-asserted-by":"publisher","first-page":"81","DOI":"10.3892\/ol.2020.11942","volume":"20","author":"L Ning","year":"2020","unstructured":"Ning L, Wang L, Zhang H, Jiao X, Chen D. Eukaryotic translation initiation factor 5A in the pathogenesis of cancers. Oncol Lett. 2020;20:81.","journal-title":"Oncol Lett"},{"key":"3499_CR63","doi-asserted-by":"publisher","first-page":"a021873","DOI":"10.1101\/cshperspect.a021873","volume":"8","author":"M Morikawa","year":"2016","unstructured":"Morikawa M, Derynck R, Miyazono K. TGF-\u03b2 and the TGF-\u03b2 family: context-dependent roles in cell and tissue physiology. Cold Spring Harb Perspect Biol. 2016;8:a021873.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"3499_CR64","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.cellsig.2006.11.008","volume":"19","author":"KR Ross","year":"2007","unstructured":"Ross KR, Corey DA, Dunn JM, Kelley TJ. SMAD3 expression is regulated by mitogen-activated protein kinase kinase-1 in epithelial and smooth muscle cells. Cell Signal. 2007;19:923\u201331.","journal-title":"Cell Signal"},{"key":"3499_CR65","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.ajhg.2010.05.017","volume":"87","author":"DL Duffy","year":"2010","unstructured":"Duffy DL, Iles MM, Glass D, Zhu G, Barrett JH, H\u00f6iom V, et al. IRF4 variants have age-specific effects on nevus count and predispose to melanoma. Am J Hum Genet. 2010;87:6\u201316.","journal-title":"Am J Hum Genet"},{"key":"3499_CR66","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41588-020-0611-8","volume":"52","author":"MT Landi","year":"2020","unstructured":"Landi MT, Bishop DT, MacGregor S, Machiela MJ, Stratigos AJ, Ghiorzo P, et al. Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility. Nat Genet. 2020;52:494\u2013504.","journal-title":"Nat Genet"},{"key":"3499_CR67","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.ophtha.2006.01.047","volume":"113","author":"T Kivel\u00e4","year":"2006","unstructured":"Kivel\u00e4 T, Eskelin S. Transformation of nevus to melanoma. Ophthalmology. 2006;113:887\u20138.e1.","journal-title":"Ophthalmology"},{"key":"3499_CR68","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.1111\/jdv.18453","volume":"36","author":"C Dessinioti","year":"2022","unstructured":"Dessinioti C, Geller AC, Stratigos AJ. A review of nevus-associated melanoma: What is the evidence? J Eur Acad Dermatol Venereol. 2022;36:1927\u201336.","journal-title":"J Eur Acad Dermatol Venereol"}],"container-title":["British Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03499-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03499-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03499-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:02:55Z","timestamp":1788282175000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41416-026-03499-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":68,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,9,20]]}},"alternative-id":["3499"],"URL":"https:\/\/doi.org\/10.1038\/s41416-026-03499-7","relation":{},"ISSN":["0007-0920","1532-1827"],"issn-type":[{"value":"0007-0920","type":"print"},{"value":"1532-1827","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"assertion":[{"value":"4 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}