Aberrant expression of TopBP1 in breast cancer
Abstract
Aims: The TopBP1 protein includes eight BRCT domains (originally identified in BRCA1) and has homology with BRCA1 over the carboxyl terminal half of the protein. The aim of this study was to determine whether TopBP1 is aberrantly expressed in breast cancer. Methods and results: Sixty‐one breast carcinomas from an unselected consecutive patient cohort were studied along with 12 samples of breast tissue from cosmetic breast reduction surgery; these were analysed immunohistochemically for TopBP1 expression using a rabbit polyclonal antibody. This antibody was validated in immunoprecipitation and immunofluorescence experiments. Immunohistochemical analysis demonstrated that TopBP1 was expressed almost exclusively in the nuclei of the normal breast epithelium. However, in a significant number of breast carcinomas TopBP1 was aberrantly expressed, as it was detected in the cytoplasm and nucleus of some tumours and exclusively in the cytoplasm of others. In two out of 61 carcinomas investigated, no TopBP1 expression was detected. Conclusions: For the first time this report demonstrates aberrant expression of the TopBP1 protein in breast carcinoma. We propose TOPBP1 as a breast cancer susceptibility gene.
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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 [19]
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Hereditary Breast Cancer and the BRCA1-Associated FANCJ/BACH1/BRIP1
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- Authors
- Going, J. J., Nixon, C., Dornan, E. S., Boner, W., Donaldson, M. M., & Morgan, I. M.
- Affiliations
- University of Glasgow (GB)
- Corresponding author
- Going, J J
- Venue
- Histopathology
- Publisher
- Wiley
- Published
- 2007-02-28
- Volume
- 50
- Issue
- 4
- Pages
- 418-424
- ISSN
- 0309-0167 (ISSN-L)
- 1365-2559
- OpenAlex
- W2115717396
- Cited by
- 35
- References
- 29
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 2 · 2021: 2 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 3 · 2012: 3
- FWCI
- 1.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Histopathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- TopBP1, breast cancer, aberrant protein expression, BRCT domain, breast epithelium, cytoplasmic expression, nuclear expression, breast cancer susceptibility genes
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Breast, Breast Neoplasms, Carrier Proteins, DNA-Binding Proteins, Female, Humans, Immunohistochemistry, Middle Aged, Nuclear Proteins, Rabbits, Reference Values, Biomarkers, Tumor, Carcinoma, Ductal, Breast, Genetic Predisposition to Disease, Mammary Glands, Human, Cell Line, Tumor
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