Identifying the BRCA1 c.-107A > T variant in Dutch patients with a tumor BRCA1 promoter hypermethylation

Abstract An inherited single nucleotide variant (SNV) in the 5′UTR of the BRCA1 gene c.-107A > T was identified to be related to BRCA1 promoter hypermethylation and a hereditary breast and ovarian cancer phenotype in two UK families. We investigated whether this BRCA1 variant was also present in a Dutch cohort of breast and ovarian cancer patients with tumor BRCA1 promoter hypermethylation. We selected all breast and ovarian cancer cases that tested positive for tumor BRCA1 promoter hypermethylation at the Netherlands Cancer Institute and Sanger sequenced the specific mutation in the tumor... Mehr ...

Verfasser: de Jong, Vincent M. T.
Pruntel, Roelof
Steenbruggen, Tessa G.
Bleeker, Fonnet E.
Nederlof, Petra
Hogervorst, Frans B. L.
linn, Sabine C.
Dokumenttyp: Artikel
Erscheinungsdatum: 2022
Reihe/Periodikum: Familial Cancer ; volume 22, issue 2, page 151-154 ; ISSN 1389-9600 1573-7292
Verlag/Hrsg.: Springer Science and Business Media LLC
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29454410
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://dx.doi.org/10.1007/s10689-022-00314-z

Abstract An inherited single nucleotide variant (SNV) in the 5′UTR of the BRCA1 gene c.-107A > T was identified to be related to BRCA1 promoter hypermethylation and a hereditary breast and ovarian cancer phenotype in two UK families. We investigated whether this BRCA1 variant was also present in a Dutch cohort of breast and ovarian cancer patients with tumor BRCA1 promoter hypermethylation. We selected all breast and ovarian cancer cases that tested positive for tumor BRCA1 promoter hypermethylation at the Netherlands Cancer Institute and Sanger sequenced the specific mutation in the tumor DNA. In total, we identified 193 tumors with BRCA1 promoter hypermethylation in 178 unique patients. The wild-type allele was identified in 100% (193/193) of sequenced tumor samples. In a large cohort of 178 patients, none had tumors harboring the previously identified c.-107A > T SNV in BRCA1 . We therefore can conclude that the germline SNV is not pervasive in patients with tumor BRCA1 promoter hypermethylation.