{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:53:09Z","timestamp":1792428789133,"version":"4.5.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National University Hospital of Iceland"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Familial Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>BAP1<\/jats:italic>\n                    tumour predisposition syndrome (\n                    <jats:italic>BAP1<\/jats:italic>\n                    -TPDS) is a hereditary cancer syndrome caused by heterozygous pathogenic germline variants in\n                    <jats:italic>BAP1<\/jats:italic>\n                    .\n                    <jats:italic>BAP1<\/jats:italic>\n                    -TPDS is associated with an increased risk for various malignant tumours, the core of which is uveal and cutaneous melanoma, malignant mesothelioma, and renal cell carcinoma. In\n                    <jats:italic>BAP1<\/jats:italic>\n                    -TPDS, the majority of disease-causing\n                    <jats:italic>BAP1<\/jats:italic>\n                    variants are null variants, although missense variants have been reported. We report a patient with\n                    <jats:italic>BAP1<\/jats:italic>\n                    -TPDS caused by the novel germline\n                    <jats:italic>BAP1<\/jats:italic>\n                    missense variant NM_004656.4:c.382G\u2009&gt;\u2009A, p.(Gly128Arg). The patient developed\n                    <jats:italic>BAP1<\/jats:italic>\n                    -inactivated melanocytic tumours, clear-cell renal cell carcinoma, and splenic hamartoma. An incidental splenic hamartoma was detected in existing tissue slides from the patient\u2019s deceased first-degree relative, who was an obligate carrier for\n                    <jats:italic>BAP1<\/jats:italic>\n                    -TPDS. In both splenic hamartomas, loss of BAP1 nuclear staining was detected in a subset of cells on immunohistochemistry. To our knowledge, this is the first report with immunohistochemical data supporting biallelic loss of\n                    <jats:italic>BAP1<\/jats:italic>\n                    as a contributing step in the development of a splenic hamartoma in a patient with\n                    <jats:italic>BAP1<\/jats:italic>\n                    -TPDS. It supports expanding the tumour spectrum of\n                    <jats:italic>BAP1<\/jats:italic>\n                    -TPDS to splenic hamartoma and possibly other benign splenic tumours.\n                  <\/jats:p>","DOI":"10.1007\/s10689-026-00538-3","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T13:07:52Z","timestamp":1771506472000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Splenic hamartoma in two related patients with BAP1 tumour predisposition syndrome caused by a novel germline BAP1 p.(Gly128Arg) missense variant"],"prefix":"10.1007","volume":"25","author":[{"given":"Kristjan Ari","family":"Ragnarsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon Gunnlaugur","family":"Jonasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudny Anna","family":"Arnadottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrun Edda","family":"Reykdal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reynir","family":"Arngrimsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigurdis","family":"Haraldsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon Johannes","family":"Jonsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"issue":"48","key":"538_CR1","doi-asserted-by":"publisher","first-page":"28643","DOI":"10.1074\/jbc.M115.661553","volume":"290","author":"S Daou","year":"2015","unstructured":"Daou S, Hammond-Martel I, Mashtalir N, Barbour H, Gagnon J, Iannantuono NVG et al (2015) The BAP1\/ASXL2 histone H2A deubiquitinase complex regulates cell proliferation and is disrupted in cancer. J Biol Chem 290(48):28643\u201328663. https:\/\/doi.org\/10.1074\/jbc.M115.661553","journal-title":"J Biol Chem"},{"issue":"1","key":"538_CR2","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1073\/pnas.1309085110","volume":"111","author":"H Yu","year":"2014","unstructured":"Yu H, Pak H, Hammond-Martel I, Ghram M, Rodrigue A, Daou S et al (2014) Tumor suppressor and deubiquitinase BAP1 promotes DNA double-strand break repair. Proc Natl Acad Sci U S A 111(1):285\u2013290. https:\/\/doi.org\/10.1073\/pnas.1309085110","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"538_CR3","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 (2018) Comprehensive study of the clinical phenotype of germline BAP1 variant-carrying families worldwide. 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