{"id":108,"date":"2023-09-25T16:00:12","date_gmt":"2023-09-25T16:00:12","guid":{"rendered":"http:\/\/sebgc.es\/blog\/?guid=6fc3dee98c23d76b9e10a2da615c0ccf"},"modified":"2023-09-25T16:00:12","modified_gmt":"2023-09-25T16:00:12","slug":"mosaic-brca1-promoter-methylation-contribution-in-hereditary-breast-ovarian-cancer-pedigrees","status":"publish","type":"post","link":"https:\/\/sebigec.es\/blog\/index.php\/2023\/09\/25\/mosaic-brca1-promoter-methylation-contribution-in-hereditary-breast-ovarian-cancer-pedigrees\/","title":{"rendered":"Mosaic BRCA1 promoter methylation contribution in hereditary breast\/ovarian cancer pedigrees"},"content":{"rendered":"<sec><st>Purpose<\/st><p>Mosaic <I>BRCA1<\/I> promoter methylation (<I>BRCA1<\/I>meth) increases the risk of early-onset breast cancer, triple-negative breast cancer and ovarian cancer. As mosaic <I>BRCA1<\/I>meth are believed to occur de novo, their role in family breast\/ovarian cancer has not been assessed.<\/p><\/sec><sec><st>Patients<\/st><p>Blood-derived DNA from 20 unrelated affected cases from families with aggregation of breast\/ovarian cancer, but with no germline pathogenic variants in <I>BRCA1<\/I>\/<I>2<\/I>, <I>PALB2<\/I> or <I>RAD51C\/D<\/I>, were screened by methylation-sensitive high-resolution melting. CpG analysis was performed by pyrosequencing on blood and buccal swab. Two probands carried a pathogenic variant in a moderate-penetrance gene (<I>ATM<\/I> and <I>BARD1<\/I>), and 8 of 18 others (44%) carried <I>BRCA1<\/I>meth (vs none of the 20 age-matched controls). Involvement of <I>BRCA1<\/I> in tumourigenesis in methylated probands was demonstrated in most tested cases by detection of a loss of heterozygosity and a homologous recombination deficiency signature. Among the eight methylated probands, two had relatives with breast cancer with detectable <I>BRCA1<\/I>meth in blood, including one with high methylation levels in two non-tumour tissues.<\/p><\/sec><sec><st>Conclusions<\/st><p>The high prevalence of mosaic <I>BRCA1<\/I>meth in patients with breast\/ovarian cancer with affected relatives, as well as this first description of a family aggregation of mosaic <I>BRCA1<\/I>meth, shows how this de novo event can contribute to hereditary breast\/ovarian cancer pedigrees.<\/p><\/sec>","protected":false},"excerpt":{"rendered":"<p>PurposeMosaic BRCA1 promoter methylation (BRCA1meth) increases the risk of early-onset breast cancer, triple-negative breast cancer and ovarian cancer. As mosaic BRCA1meth are believed to occur de novo, their role in family breast\/ovarian cancer has no&#8230;<\/p>\n","protected":false},"author":0,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[6,8],"tags":[],"class_list":["post-108","post","type-post","status-publish","format-standard","hentry","category-articulos","category-jmg-first"],"_links":{"self":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/108","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/types\/post"}],"replies":[{"embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/comments?post=108"}],"version-history":[{"count":1,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/108\/revisions"}],"predecessor-version":[{"id":109,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/posts\/108\/revisions\/109"}],"wp:attachment":[{"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/media?parent=108"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/categories?post=108"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/sebigec.es\/blog\/index.php\/wp-json\/wp\/v2\/tags?post=108"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}