{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:40:34Z","timestamp":1792518034656,"version":"4.5.0"},"reference-count":28,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,7,5]],"date-time":"2018-07-05T00:00:00Z","timestamp":1530748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["IS-BRC-1215-20007"],"award-info":[{"award-number":["IS-BRC-1215-20007"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2018,8]]},"DOI":"10.1016\/j.ajhg.2018.07.002","type":"journal-article","created":{"date-parts":[[2018,8,2]],"date-time":"2018-08-02T10:41:42Z","timestamp":1533206502000},"page":"213-220","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":89,"title":["A Dominantly Inherited 5\u2032 UTR Variant Causing Methylation-Associated Silencing of BRCA1 as a Cause of Breast and Ovarian Cancer"],"prefix":"10.1016","volume":"103","author":[{"given":"D.Gareth R.","family":"Evans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke M.","family":"van Veen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen J.","family":"Byers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie M.","family":"Ellingford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenda","family":"Beaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Santoyo-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Aitman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Eccles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona I.","family":"Lalloo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Newman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2018.07.002_bib1","first-page":"11","article-title":"Cancer statistics, 2013","volume":"63","author":"Siegel","year":"2013","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.ajhg.2018.07.002_bib2","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1054\/bjoc.2000.1407","article-title":"Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases","volume":"83","year":"2000","journal-title":"Br. J. Cancer"},{"key":"10.1016\/j.ajhg.2018.07.002_bib3","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1200\/JCO.2011.39.8545","article-title":"BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: A report from the Australian Ovarian Cancer Study Group","volume":"30","author":"Alsop","year":"2012","journal-title":"J.\u00a0Clin. Oncol."},{"key":"10.1016\/j.ajhg.2018.07.002_bib4","doi-asserted-by":"crossref","first-page":"R92","DOI":"10.1186\/bcr3493","article-title":"Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer","volume":"15","author":"Eccles","year":"2013","journal-title":"Breast Cancer Res."},{"key":"10.1016\/j.ajhg.2018.07.002_bib5","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1056\/NEJMsr1501341","article-title":"Gene-panel sequencing and the prediction of breast-cancer risk","volume":"372","author":"Easton","year":"2015","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2018.07.002_bib6","doi-asserted-by":"crossref","first-page":"7006","DOI":"10.1158\/0008-5472.CAN-08-0599","article-title":"The relative contribution of point mutations and genomic rearrangements in BRCA1 and BRCA2 in high-risk breast cancer families","volume":"68","author":"Palma","year":"2008","journal-title":"Cancer Res."},{"key":"10.1016\/j.ajhg.2018.07.002_bib7","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/ejhg.2016.57","article-title":"Sensitivity of BRCA1\/2 testing in high-risk breast\/ovarian\/male breast cancer families: Little contribution of comprehensive RNA\/NGS panel testing","volume":"24","author":"Byers","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2018.07.002_bib8","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0140-6736(10)60892-6","article-title":"Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: A proof-of-concept trial","volume":"376","author":"Tutt","year":"2010","journal-title":"Lancet"},{"key":"10.1016\/j.ajhg.2018.07.002_bib9","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1056\/NEJMra023075","article-title":"Gene silencing in cancer in association with promoter hypermethylation","volume":"349","author":"Herman","year":"2003","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2018.07.002_bib10","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1038\/sj.onc.1202086","article-title":"Aberrant methylation of the BRCA1 CpG island promoter is associated with decreased BRCA1 mRNA in sporadic breast cancer cells","volume":"17","author":"Rice","year":"1998","journal-title":"Oncogene"},{"key":"10.1016\/j.ajhg.2018.07.002_bib11","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1093\/jnci\/92.7.564","article-title":"Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors","volume":"92","author":"Esteller","year":"2000","journal-title":"J.\u00a0Natl. Cancer Inst."},{"key":"10.1016\/j.ajhg.2018.07.002_bib12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4161\/epi.3.3.6387","article-title":"Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors","volume":"3","author":"Tapia","year":"2008","journal-title":"Epigenetics"},{"key":"10.1016\/j.ajhg.2018.07.002_bib13","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.clbc.2015.06.009","article-title":"Epigenetic inactivation of BRCA1 through promoter hypermethylation and its clinical importance in triple-negative breast cancer","volume":"15","author":"Yamashita","year":"2015","journal-title":"Clin. Breast Cancer"},{"key":"10.1016\/j.ajhg.2018.07.002_bib14","doi-asserted-by":"crossref","first-page":"4669","DOI":"10.1093\/hmg\/dds308","article-title":"Constitutive promoter methylation of BRCA1 and RAD51C in patients with familial ovarian cancer and early-onset sporadic breast cancer","volume":"21","author":"Hansmann","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.ajhg.2018.07.002_bib15","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1056\/NEJMoa064522","article-title":"Inheritance of a cancer-associated MLH1 germ-line epimutation","volume":"356","author":"Hitchins","year":"2007","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.ajhg.2018.07.002_bib16","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1038\/ng.283","article-title":"Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3\u2032 exons of TACSTD1","volume":"41","author":"Ligtenberg","year":"2009","journal-title":"Nat. Genet."},{"key":"10.1016\/j.ajhg.2018.07.002_bib17","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.4161\/epi.22561","article-title":"BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer","volume":"7","author":"Stefansson","year":"2012","journal-title":"Epigenetics"},{"key":"10.1016\/j.ajhg.2018.07.002_bib18","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1136\/jmg.2003.017996","article-title":"A new scoring system for the chances of identifying a BRCA1\/2 mutation outperforms existing models including BRCAPRO","volume":"41","author":"Evans","year":"2004","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ajhg.2018.07.002_bib19","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1136\/jmedgenet-2017-104584","article-title":"Pathology update to the Manchester Scoring System based on testing in over 4000 families","volume":"54","author":"Evans","year":"2017","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ajhg.2018.07.002_bib20","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1089\/gte.2006.0518","article-title":"The use of ancestral haplotypes in the molecular diagnosis of familial breast cancer","volume":"11","author":"Frosk","year":"2007","journal-title":"Genet. Test."},{"key":"10.1016\/j.ajhg.2018.07.002_bib21","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nature19057","article-title":"Analysis of protein-coding genetic variation in 60,706 humans","volume":"536","author":"Lek","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.ajhg.2018.07.002_bib22","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1126\/science.7545954","article-title":"A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1","volume":"266","author":"Miki","year":"1994","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2018.07.002_bib23","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13148-016-0207-4","article-title":"Defining the criteria for identifying constitutional epimutations","volume":"8","author":"Sloane","year":"2016","journal-title":"Clin. Epigenetics"},{"key":"10.1016\/j.ajhg.2018.07.002_bib24","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ccr.2011.07.003","article-title":"Dominantly inherited constitutional epigenetic silencing of MLH1 in a cancer-affected family is linked to a single nucleotide variant within the 5\u2019UTR","volume":"20","author":"Hitchins","year":"2011","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ajhg.2018.07.002_bib25","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1136\/jmedgenet-2017-104744","article-title":"Comprehensive analysis of the MLH1 promoter region in 480 patients with colorectal cancer and 1150 controls reveals new variants including one with a heritable constitutional MLH1 epimutation","volume":"55","author":"Morak","year":"2018","journal-title":"J.\u00a0Med. Genet."},{"key":"10.1016\/j.ajhg.2018.07.002_bib26","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrc4001","article-title":"Constitutional epimutation as a mechanism for cancer causality and heritability?","volume":"15","author":"Hitchins","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"10.1016\/j.ajhg.2018.07.002_bib27","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/1471-2407-8-155","article-title":"Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: Risks of breast\/ovarian cancer quoted should reflect the cancer burden in the family","volume":"8","author":"Evans","year":"2008","journal-title":"BMC Cancer"},{"key":"10.1016\/j.ajhg.2018.07.002_bib28","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s10689-011-9506-2","article-title":"Risk of cancer other than breast or ovarian in individuals with BRCA1 and BRCA2 mutations","volume":"11","author":"Moran","year":"2012","journal-title":"Fam. Cancer"}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929718302295?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929718302295?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T07:14:02Z","timestamp":1757574842000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929718302295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,8]]}},"alternative-id":["S0002929718302295"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2018.07.002","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2018,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"A Dominantly Inherited 5\u2032 UTR Variant Causing Methylation-Associated Silencing of BRCA1 as a Cause of Breast and Ovarian Cancer","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2018.07.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 The Authors.","name":"copyright","label":"Copyright"}]}}