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

Autor: de Jong VMT; Department of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, Netherlands., Pruntel R; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands., Steenbruggen TG; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands., Bleeker FE; Department of Clinical Genetics, The Netherlands Cancer Institute, Amsterdam, Netherlands., Nederlof P; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands., Hogervorst FBL; Department of Pathology, The Netherlands Cancer Institute, Amsterdam, Netherlands., Linn SC; Department of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066CX, Amsterdam, Netherlands. s.linn@nki.nl.; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands. s.linn@nki.nl.; Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands. s.linn@nki.nl.
Jazyk: angličtina
Zdroj: Familial cancer [Fam Cancer] 2023 Apr; Vol. 22 (2), pp. 151-154. Date of Electronic Publication: 2022 Sep 16.
DOI: 10.1007/s10689-022-00314-z
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE