White Blood Cell <i>BRCA1</i> Promoter Methylation Status and Ovarian Cancer Risk: A Perspective
Authors: Alexander Dobrovic
Journal: Annals of Internal Medicine (2018)

Editorials6 March 2018White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk: A PerspectiveAlexander Dobrovic, PhDAlexander Dobrovic, PhDOlivia Newton-John Cancer Research Institute, Heidelberg, La Trobe University, Bundoora, and University of Melbourne, Parkville, Victoria, Australia (A.D.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M17-3340 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail An increasing number of researchers consider changes in DNA methylation at the promoter regions of specific loci to be as important as genetic events in the initiation of cancer (1). The seminal publication that implicated promoter region methylation (hereafter referred to as methylation) as an initiating event in carcinogenesis was the report that methylation of a familial cancer driver, the RB1 tumor suppressor gene, was observed in nonfamilial retinoblastomas (2). Inactivation of the gene by epigenetic silencing, leading to functional loss of activity, thus was an alternative to mutational inactivation. It then became apparent that other genes that recurrently mutated ...References1. Ushijima T, Asada K. Aberrant DNA methylation in contrast with mutations. Cancer Sci. 2010;101:300-5. [PMID: 19958364] doi:10.1111/j.1349-7006.2009.01434.x CrossrefMedlineGoogle Scholar2. Greger V, Passarge E, Höpping W, Messmer E, Horsthemke B. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet. 1989;83:155-8. [PMID: 2550354] CrossrefMedlineGoogle Scholar3. Bianco T, Chenevix-Trench G, Walsh DC, Cooper JE, Dobrovic A. Tumour-specific distribution of BRCA1 promoter region methylation supports a pathogenetic role in breast and ovarian cancer. Carcinogenesis. 2000;21:147-51. [PMID: 10657950] CrossrefMedlineGoogle Scholar4. Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, et al. Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 2000;92:564-9. [PMID: 10749912] CrossrefMedlineGoogle Scholar5. Gazzoli I, Loda M, Garber J, Syngal S, Kolodner RD. A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor. Cancer Res. 2002;62:3925-8. [PMID: 12124320] MedlineGoogle Scholar6. Snell C, Krypuy M, Wong EM, Loughrey MB, Dobrovic A; kConFab investigators. BRCA1 promoter methylation in peripheral blood DNA of mutation negative familial breast cancer patients with a BRCA1 tumour phenotype. Breast Cancer Res. 2008;10:R12. [PMID: 18269736] doi:10.1186/bcr1858 CrossrefMedlineGoogle Scholar7. Wong EM, Southey MC, Fox SB, Brown MA, Dowty JG, Jenkins MA, et al. Constitutional methylation of the BRCA1 promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer. Cancer Prev Res (Phila). 2011;4:23-33. [PMID: 20978112] doi:10.1158/1940-6207.CAPR-10-0212 CrossrefMedlineGoogle Scholar8. Lønning PE, Berge EO, Bjørnslett M, Minsaas L, Chrisanthar R, Høberg-Vetti H, et al. White blood cell BRCA1 promoter methylation status and ovarian cancer risk. Ann Intern Med. 2018;168:326-34. doi:10.7326/M16-2011 LinkGoogle Scholar9. Dobrovic A, Mikeska T, Alsop K, Candiloro I, George J, Mitchell G, Bowtell D. Constitutional BRCA1 methylation is a major predisposition factor for high-grade serous ovarian cancer. Cancer Res. 2014;74 Suppl 19 290. Google Scholar10. Issa JP, Garber JE. Time to think outside the (genetic) box. Cancer Prev Res (Phila). 2011;4:6-8. [PMID: 21205738] doi:10.1158/1940-6207.CAPR-10-0348 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Olivia Newton-John Cancer Research Institute, Heidelberg, La Trobe University, Bundoora, and University of Melbourne, Parkville, Victoria, Australia (A.D.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-3340.Corresponding Author: Alexander Dobrovic, PhD, Olivia Newton-John Cancer Research Institute, Studley Road, Heidelberg, Victoria 3084, Australia; e-mail, alex.[email protected]org.au.This article was published at Annals.org on 16 January 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoWhite Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk Per E. Lønning , Elisabet O. Berge , Merete Bjørnslett , Laura Minsaas , Ranjan Chrisanthar , Hildegunn Høberg-Vetti , Cécile Dulary , Florence Busato , Silje Bjørneklett , Christine Eriksen , Reidun Kopperud , Ulrika Axcrona , Ben Davidson , Line Bjørge , Gareth Evans , Anthony Howell , Helga B. Salvesen , Imre Janszky , Kristian Hveem , Pål R. Romundstad , Lars J. Vatten , Jörg Tost , Anne Dørum , and Stian Knappskog Metrics Cited byUCP1 modulates immune infiltration level and survival outcome in ovarian cancer patientsElectronic characteristics of BRCA1 mutations in DNA 6 March 2018Volume 168, Issue 5Page: 365-366KeywordsAllelesBreast cancerCancer geneticsCellsHeterozygosityMethylationOvarian cancerPathogenesisTumor suppressor genesWhite blood cells ePublished: 16 January 2018 Issue Published: 6 March 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...