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

Vincent M.T. de Jong; Roelof Pruntel; Tessa G. Steenbruggen; Fonnet E. Bleeker; Petra Nederlof; Frans B.L. Hogervorst; Sabine C. linn

doi:10.1007/s10689-022-00314-z

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

Vincent M.T. de Jong, Roelof Pruntel, Tessa G. Steenbruggen, Fonnet E. Bleeker, Petra Nederlof, Frans B.L. Hogervorst, Sabine C. linn^*

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	151-154
Number of pages	4
Journal	Familial cancer
Volume	22
Issue number	2
DOIs	https://doi.org/10.1007/s10689-022-00314-z
Publication status	Published - Apr 2023

Keywords

BRCA1
Breast cancer
Methylation

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title = "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 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.",

keywords = "BRCA1, Breast cancer, Methylation",

author = "{de Jong}, {Vincent M.T.} and Roelof Pruntel and Steenbruggen, {Tessa G.} and Bleeker, {Fonnet E.} and Petra Nederlof and Hogervorst, {Frans B.L.} and linn, {Sabine C.}",

note = "Funding Information: SCL reports grants from ZonMw, the Dutch Cancer Society, and A Sister{\textquoteright}s Hope during the conduct of the study. SCL is an advisory board member for Cergentis, and IBM, and received institutional research support from Agendia, AstraZeneca, Eurocept-pharmaceuticals, Genentech, Novartis, Pfizer, Roche, Tesaro, and Immunomedics. In addition, SCL received institutional non-financial support from AstraZeneca, Genentech, Novartis, Roche, Tesaro, and Immunomedics and institutional educational financial support from Bayer and Daiichi-Sankyo outside of this study. All other authors declare no competing interest. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2023",

month = apr,

doi = "10.1007/s10689-022-00314-z",

language = "English",

volume = "22",

pages = "151--154",

journal = "Familial cancer",

issn = "1389-9600",

publisher = "Springer Netherlands",

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T1 - Identifying the BRCA1 c.-107A > T variant in Dutch patients with a tumor BRCA1 promoter hypermethylation

AU - de Jong, Vincent M.T.

AU - Pruntel, Roelof

AU - Steenbruggen, Tessa G.

AU - Bleeker, Fonnet E.

AU - Nederlof, Petra

AU - Hogervorst, Frans B.L.

AU - linn, Sabine C.

N1 - Funding Information: SCL reports grants from ZonMw, the Dutch Cancer Society, and A Sister’s Hope during the conduct of the study. SCL is an advisory board member for Cergentis, and IBM, and received institutional research support from Agendia, AstraZeneca, Eurocept-pharmaceuticals, Genentech, Novartis, Pfizer, Roche, Tesaro, and Immunomedics. In addition, SCL received institutional non-financial support from AstraZeneca, Genentech, Novartis, Roche, Tesaro, and Immunomedics and institutional educational financial support from Bayer and Daiichi-Sankyo outside of this study. All other authors declare no competing interest. Publisher Copyright: © 2022, The Author(s).

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

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KW - Methylation

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JO - Familial cancer

JF - Familial cancer

IS - 2

ER -

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

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