The DOI matches its Crossref record; 92 of the 93 references it cites were found in a registry or an index.
BRCA1 and BRCA2 and the genetics of breast and ovarian cancer
Abstract
Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose individuals to breast and ovarian cancers. Progress in determining the function of BRCA1 and BRCA2 suggests that they are involved in two fundamental cellular processes: DNA damage repair and transcriptional regulation. We evaluate current knowledge of BRCA1 and BRCA2 functions to explain why mutations in BRCA1 and BRCA2 lead specifically to breast and ovarian cancer. The BRCA1 and BRCA2 genes contain unusually high densities of repetitive elements. These features of the BRCAs genomic regions contribute to chromosomal instability of these genes. We propose that somatic alterations of BRCA1 and BRCA2 are common and driven by rearrangements between repetitive elements. Inherited and somatic mutations occur in BRCA1 and BRCA2; virtually all somatic mutations are the result of large genomic rearrangements. What are the consequences of such large somatic mutations of BRCA1 and BRCA2 in women with or without inherited mutations? The breast and ovary are estrogen-responsive tissues. Beginning in puberty, the breast epithelium proliferates rapidly in response to fluctuating levels of estrogen. We present a genetic model outlining how BRCA-deficient cells may gain uncontrolled proliferation leading to tumor formation. Central to this model of BRCA-mediated tumorigenesis are estrogen-mediated proliferation of breast and ovarian epithelium and the distinctive genomic context of the BRCA genes.
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“Mendelian subtypes of common diseases [such as breast cancer (15), hypertension (16), and diabetes (17)] were elucidated, but mutations in these genes explained few cases in the population.”
From Genetic Mapping in Human Disease (2008) · cites this paper as [15]
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A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1
Miki, Y., Swensen, J. J., Shattuck-Eidens, D. M., Futreal, P. A., Harshman, K., Tavtigian, S. V., Liu, Q., Cochran, C., Bennett, L. M., Ding, W., et al. (1994) · Science · doi:10.1126/science.7545954 · Cited by 6,069
Identification of the breast cancer susceptibility gene BRCA2
Wooster, R., Bignell, G. R., Lancaster, J., Swift, S., Seal, S., Mangion, J., Collins, N., Gregory, S. G., Gumbs, C. E., Micklem, G., et al. (1995) · Nature · doi:10.1038/378789a0 · Cited by 3,645
Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21
Hall, J., Lee, M. K., Newman, B. M., Morrow, J. E., Anderson, L. A., Huey, B., & King, M. (1990) · Science · doi:10.1126/science.2270482 · Cited by 2,544
A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage
Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., & Bonner, W. M. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00610-2 · Cited by 2,098
Localization of a Breast Cancer Susceptibility Gene, BRCA2 , to Chromosome 13q12-13
Wooster, R., Neuhausen, S. L., Mangion, J., Quirk, Y., Ford, D., Collins, N., Nguyen, K. N., Seal, S., Tran, T. D., Averill, D., et al. (1994) · Science · doi:10.1126/science.8091231 · Cited by 1,918
Risks of cancer in BRCA1-mutation carriers
FORD, D. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91578-4 · Cited by 1,850
Association of BRCA1 with Rad51 in Mitotic and Meiotic Cells
Scully, R., Chen, J., Plug, A., Xiao, Y., Weaver, D., Feunteun, J., Ashley, T., & Livingston, D. M. (1997) · Cell · doi:10.1016/s0092-8674(00)81847-4 · Cited by 1,459
Cancer risks in BRCA2 mutation carriers.
Olsson, H. (1999) · Journal of the National Cancer Institute · doi:10.1093/jnci/91.15.1310 · Cited by 1,404
BRCA1 mutations in primary breast and ovarian carcinomas.
Futreal, P., Liu, Q., Shattuck-Eidens, D., Cochran, C., Harshman, K., Tavtigian, S., Bennett, L., Haugen-Strano, A., Swensen, J., & Miki, Y. (1994) · Science · doi:10.1126/science.7939630 · Cited by 1,378
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Maintenance Olaparib for Germline BRCA -Mutated Metastatic Pancreatic Cancer
Golan, T., Hammel, P., Reni, M., Van Cutsem, E., Macarulla, T., Hall, M. J., Park, J.-O., Hochhauser, D., Arnold, D., Oh, D.-Y., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1903387 · Cited by 2,302
Genetic Mapping in Human Disease
Altshuler, D., Daly, M. J., & Lander, E. S. (2008) · Science · doi:10.1126/science.1156409 · Cited by 1,452
Gelmon, K. A., Tischkowitz, M. D., MacKay, H. J., Swenerton, K. D., Robidoux, A., Tonkin, K. S., Hirte, H. W., Huntsman, D. D., Clemons, M. J., Gilks, C. B., et al. (2011) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70214-5 · Cited by 1,130
Molecular views of recombination proteins and their control
West, S. C. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1127 · Cited by 977
Control of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2
Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F. J., & Livingston, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.022 · Cited by 861
Metadata
- Authors
- Welcsh, P. L.
- Affiliations
- University of Washington (US)
- Corresponding author
- Welcsh, P. L.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-04-01
- Volume
- 10
- Issue
- 7
- Pages
- 705-713
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2124371549
- Cited by
- 648
- References
- 93
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 25 · 2023: 19 · 2022: 19 · 2021: 26 · 2020: 27 · 2019: 33 · 2018: 30 · 2017: 36 · 2016: 34 · 2015: 31 · 2014: 29 · 2013: 25 · 2012: 17
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Human Molecular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca027632-22)
- National Cancer Institute (CA27632)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- BRCA1, BRCA2, hereditary breast cancer, hereditary ovarian cancer, germline mutations, somatic mutations, DNA repair, transcriptional regulation, repetitive elements, chromosomal instability, genome rearrangement, carcinogenesis, tumor suppressor
- MeSH terms
- Breast Neoplasms, Cell Division, Chromosomes, Estrogens, Female, Humans, Models, Biological, Mutation, Neoplasm Proteins, Ovarian Neoplasms, Repetitive Sequences, Nucleic Acid, Transcription Factors, Gene Deletion, Genes, BRCA1, Genetic Predisposition to Disease, BRCA2 Protein
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