{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T05:12:55Z","timestamp":1783228375653,"version":"3.54.6"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,4,23]],"date-time":"2019-04-23T00:00:00Z","timestamp":1555977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["K08EY022672"],"award-info":[{"award-number":["K08EY022672"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Uveal melanoma (UM) is the most common phenotype in patients with germline <jats:italic>BAP1<\/jats:italic> mutation. This study aimed to identify selection criteria for <jats:italic>BAP1<\/jats:italic> germline testing and assessed the role of large deletion\/duplication and epigenetic inactivation. One hundred seventy\u2010two UM patients with high risk of hereditary cancer were included. Germline variants in <jats:italic>BAP1<\/jats:italic> were assessed by direct sequencing and large deletion\/duplication by multiplex ligation\u2010dependent probe amplification. <jats:italic>BAP1<\/jats:italic> expression in unaffected choroid tissue from a patient with UM was assessed by quantitative RT\u2010PCR and methylation by pyrosequencing. Twenty\u2010eight patients had one or more germline sequence variants in <jats:italic>BAP1<\/jats:italic>; seven of these were pathogenic. One hundred forty patients were assessed for large deletion\/duplication and in one <jats:italic>BAP1<\/jats:italic> whole gene deletion was detected. In total, eight patients (4.7%) had pathogenic alterations in <jats:italic>BAP1<\/jats:italic> with the highest frequencies of in patients with a personal\/family history of \u22652 <jats:italic>BAP1\u2010<\/jats:italic>related cancers 6\/16 (38%), age of onset &lt;35\u2009years 4\/21 (19%) and familial UM 6\/34 (18%). One of 19 non\u2010tumor choroid tissues tested showed uncharacteristically low expression as compared to the controls decrease in <jats:italic>BAP1<\/jats:italic> RNA expression but no evidence of constitutional promotor hypermethylation was detected. UM patients with a strong personal or family history of cancers associated with <jats:italic>BAP1<\/jats:italic>, early age of onset and familial UM should be assessed for germline variants in <jats:italic>BAP1,<\/jats:italic> including large deletions.<\/jats:p>","DOI":"10.1002\/gcc.22752","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T09:17:40Z","timestamp":1552987060000},"page":"650-656","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Germline large deletion of <i>BAP1<\/i> and decreased expression in non\u2010tumor choroid in uveal melanoma patients with high risk for inherited cancer"],"prefix":"10.1002","volume":"58","author":[{"given":"Getachew","family":"Boru","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science Havener Eye Institute, The Ohio State University Columbus  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Grosel","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science Havener Eye Institute, The Ohio State University Columbus  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pilarski","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Internal Medicine The Ohio State University Columbus  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Stautberg","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Internal Medicine The Ohio State University Columbus  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Massengill","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science Havener Eye Institute, The Ohio State University Columbus  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Jeter","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Internal Medicine The Ohio State University Columbus  Columbus Ohio"},{"name":"Division of Medical Oncology The Ohio State University Comprehensive Cancer Center  Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun","family":"Singh","sequence":"additional","affiliation":[{"name":"Cole Eye Institute Department of Ophthalmic Oncology, Cleveland Clinic  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan J.","family":"Marino","sequence":"additional","affiliation":[{"name":"Cole Eye Institute Department of Ophthalmic Oncology, Cleveland Clinic  Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"McElroy","sequence":"additional","affiliation":[{"name":"Center 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