Identification of a common polymorphism in the TopBP1 gene associated with hereditary susceptibility to breast and ovarian cancer
Abstract
Besides BRCA1 and BRCA2 other genes are also likely to be involved in hereditary predisposition to breast and/or ovarian cancer. TopBP1 (topoisomerase IIbeta binding protein 1) displays sequence homology as well as functional similarities with BRCA1, and the two proteins have been suggested to function partly in the same cellular processes. TopBP1 is crucial for DNA damage and replication checkpoint controls. Based on its biological significance, we reasoned that TopBP1 is a plausible susceptibility gene for hereditary breast and/or ovarian cancer and therefore screened affected index cases from 125 Finnish cancer families for germline changes by conformation sensitive gel electrophoresis (CSGE). Altogether 19 different sequence alterations were detected. A novel heterozygous Arg309Cys variant was observed at elevated frequency in the familial cancer cases compared to healthy controls (15.2% versus 7.0%; P=0.002). Current results suggest that Arg309Cys is a commonly occurring germline alteration possibly associated with a slightly increased breast and/or ovarian cancer risk. This is the first study reporting mutation screening of the TopBP1 gene in a familial cancer material.
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CHEK2, ATM, NBS1, RAD50, TOPBP1, and RAD51C are mutated in breast cancer patients.
“Correspondingly, these and other genes functioning in the DNA damage response, such as CHEK2, ATM, NBS1, RAD50, TOPBP1 and RAD51C, are mutated in breast cancer patients [12–21].”
From Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1 (2011) · cites this paper as [20]
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Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1
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- Authors
- Karppinen, S.-M., Erkko, H., Reini, K., Pospiech, H., Heikkinen, K., Rapakko, K., Syväoja, J. E., & Winqvist, R.
- Affiliations
- Oulu University Hospital (FI)
- University of Oulu (FI)
- University of Eastern Finland (FI)
- Corresponding author
- Winqvist, Robert
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 42
- Issue
- 15
- Pages
- 2647-2652
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W1979087808
- Cited by
- 42
- References
- 32
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2019: 1 · 2018: 1 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 3
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Academy of Finland
- Oulun Yliopisto
- U.S. Bureau of Land Management
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- TopBP1, hereditary breast cancer, hereditary ovarian cancer, cancer susceptibility genes, germline mutations, DNA damage checkpoint, S-phase checkpoint, mutation detection
- MeSH terms
- Adult, Breast Neoplasms, Carrier Proteins, DNA-Binding Proteins, Female, Humans, Mutation, Neoplasm Proteins, Nuclear Proteins, Ovarian Neoplasms, Pedigree, Polymorphism, Genetic, Risk Factors, Tumor Cells, Cultured, Blotting, Western, Sequence Analysis, Genetic Predisposition to Disease
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