{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T22:43:05Z","timestamp":1789684985399,"version":"4.0.1"},"reference-count":12,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T00:00:00Z","timestamp":1532908800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>The <jats:italic>BAP1<\/jats:italic>\u2010tumor predisposition syndrome (<jats:italic>BAP1<\/jats:italic>\u2010TPDS) has been recently identified to predispose patients to a variety of cancers and preneoplastic lesions. About 130 unrelated probands have been identified worldwide; however, the impact of the syndrome is suspected to be much larger given the diversity of the cancer phenotype. To evaluate the frequency of germline <jats:italic>BAP1<\/jats:italic> mutations in the general and cancer populations, we analyzed the Exome Aggregation Consortium (ExAC), a database that contains 53105 exomes of unrelated individuals unaffected by cancer (general population) and exomes of 7601 unrelated individuals affected by cancer provided by the Cancer Genome Atlas (TCGA, cancer subjects). <jats:italic>BAP1<\/jats:italic> null variants were seen at much higher frequency in the cancer subjects (0.0526%) compared to the general population (0.00188%) with a relative risk of 27.93 and (<jats:italic>P<\/jats:italic>\u2009=\u20090.0011, [95% CI: 3.122\u2010249.883], Fisher's exact test). We also studied a reported <jats:italic>BAP1<\/jats:italic> null variant, c.1203T\u2009&gt;\u2009G, p.T401* (rs200156887), observed commonly in the general population. Sequencing and restriction fragment polymorphism of the RT\u20104 cell line that contains this variant revealed that it is in fact a 3bp deletion\/insertion, c.1201_1203delinsGAG, a likely benign missense alteration p.Y401E explaining the relative high frequency of this variant in the general population. In conclusion, germline null mutations in <jats:italic>BAP1<\/jats:italic> have a significantly higher frequency in cancer patients than the general population. Given the low frequency of reported families with <jats:italic>BAP1<\/jats:italic>\u2010TPDS, our results suggest that the syndrome is underreported especially in patients with cancer.<\/jats:p>","DOI":"10.1002\/gcc.7","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T08:52:32Z","timestamp":1526374352000},"page":"478-481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Analysis of the exome aggregation consortium (ExAC) database suggests that the <i>BAP1\u2010<\/i>tumor predisposition syndrome is underreported in cancer patients"],"prefix":"10.1002","volume":"57","author":[{"given":"James B.","family":"Massengill","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The Ohio State University Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klarke M.","family":"Sample","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Ohio State University 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 Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"McElroy","sequence":"additional","affiliation":[{"name":"Center for Biostatistics, Department of Biomedical Informatics The Ohio State University Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick H.","family":"Davidorf","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Ohio State University Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen M.","family":"Cebulla","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Ohio State University Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-7894","authenticated-orcid":false,"given":"Mohamed H.","family":"Abdel\u2010Rahman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The Ohio State University Columbus Ohio"},{"name":"Division of Human Genetics, Department of Internal Medicine The Ohio State University Columbus Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12630"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.012"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.910"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.912"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100156"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature19057"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_5_9_1","article-title":"Predicting functional effect of human missense mutations using PolyPhen","volume":"7","author":"Adzhubei I","year":"2013","journal-title":"Curr Protoc Hum Genet. Chap."},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-016-9865-9"},{"key":"e_1_2_5_12_1","unstructured":"PilarskiR RaiK CebullaC Abdel\u2010RahmanM.BAP1 tumor predisposition syndrome. 2016 Oct 13. In: Adam MP Ardinger HH Pagon RA et al. eds. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington Seattle; 1993-2018. Available from:https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK390611\/"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.10.002"}],"container-title":["Genes, Chromosomes and Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgcc.7","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gcc.7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:51:28Z","timestamp":1694998288000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gcc.7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,30]]},"references-count":12,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1002\/gcc.7"],"URL":"https:\/\/doi.org\/10.1002\/gcc.7","archive":["Portico"],"relation":{},"ISSN":["1045-2257","1098-2264"],"issn-type":[{"value":"1045-2257","type":"print"},{"value":"1098-2264","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,30]]},"assertion":[{"value":"2018-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}