{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:40:59Z","timestamp":1791931259927,"version":"4.3.4"},"reference-count":26,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"3","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n PURPOSE<\/jats:title>\n \n BRCA1<\/jats:italic>\n promoter methylation (\n BRCA1<\/jats:italic>\n meth) affects 20%-27% of triple-negative breast cancer (TNBC) and ovarian cancer (OvCa) and has therapeutic predictive value in both cancer types.\n BRCA1<\/jats:italic>\n meth is established during early embryonic development as a constitutional event, and its detection in the peripheral blood cells of unaffected women associates with increased risk for breast cancer and OvCa. Thus, facile and sensitive assessment of\n BRCA1<\/jats:italic>\n meth is an important component for both risk assessment and the therapeutic management of these cancer types.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We used the GRAIL circulating cell-free DNA (cfDNA)\u2013based targeted methylation platform to quantify\n BRCA1<\/jats:italic>\n meth in cfDNA (cf\n BRCA1<\/jats:italic>\n meth) from plasma samples of individuals with and without cancer.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Detection of cf\n BRCA1<\/jats:italic>\n meth was accurate and sensitive, with an empirical LoD\n 95<\/jats:sub>\n of 0.0081. cf\n BRCA1<\/jats:italic>\n meth was found in 4.1% (113\/2,790) of individuals without cancer, and it was significantly more prevalent in females compared with males (4.8%\n v<\/jats:italic>\n 2.9%,\n P<\/jats:italic>\n = .016), suggesting that the dynamics of\n BRCA1<\/jats:italic>\n promoter methylation and its consequences for cancer development may differ by sex. In a pan-cancer cohort comprising 2,849 patients and representing 15 tissue types, cf\n BRCA1<\/jats:italic>\n meth was enriched only in TNBC (15.2%,\n P<\/jats:italic>\n = .001) and OvCa (13.9%,\n P<\/jats:italic>\n = .014). Importantly, in these cf\n BRCA1<\/jats:italic>\n meth-positive cases, the fraction of cf\n BRCA1<\/jats:italic>\n meth was correlated with a methylation-based estimate of tumor burden.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSION<\/jats:title>\n \n Our findings demonstrate that\n BRCA1<\/jats:italic>\n meth can be robustly detected using cfDNA assessment both as a constitutional event in noncancer samples and as a metric of\n BRCA1<\/jats:italic>\n meth tumor burden in individuals with\n BRCA1<\/jats:italic>\n meth cancers. Therefore, the GRAIL assay provides a single quantitative platform that can be used to explore the role of\n BRCA1<\/jats:italic>\n meth in cancer risk and therapeutic response.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1200\/po-25-00854","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:13:02Z","timestamp":1773087182000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence of\n BRCA1<\/i>\n Promoter Methylation in Cohorts of Individuals With and Without Cancer Assessed by Circulating Cell-Free DNA"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4293-4795","authenticated-orcid":true,"given":"Edison T.","family":"Liu","sequence":"first","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1049-211X","authenticated-orcid":true,"given":"Margaret","family":"Antonio","sequence":"additional","affiliation":[{"name":"GRAIL, Inc, Menlo Park, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9246-0765","authenticated-orcid":true,"given":"Tracy","family":"Nance","sequence":"additional","affiliation":[{"name":"GRAIL, Inc, Menlo Park, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7209-251X","authenticated-orcid":true,"given":"Francesca","family":"Menghi","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory for Genomic Medicine, Farmington, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_10_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11412"},{"key":"e_1_3_10_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abn1926"},{"key":"e_1_3_10_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14410"},{"key":"e_1_3_10_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0582-4"},{"key":"e_1_3_10_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2022.3846"},{"key":"e_1_3_10_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17537-2"},{"key":"e_1_3_10_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01262-8"},{"key":"e_1_3_10_9_2","article-title":"Constitutional epimutations: From rare events toward major cancer risk factors?","author":"Lonning PE","unstructured":"Lonning PE, Nikolaienko O, Knappskog S: Constitutional epimutations: From rare events toward major cancer risk factors? 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