The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities
Open accessAbstract
Background: Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. Methods: A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Results: Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. Conclusion: High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.
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2 retracted
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RetractedWAF1, a potential mediator of p53 tumor suppression
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Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
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A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1
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Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21
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Localization of a Breast Cancer Susceptibility Gene, BRCA2 , to Chromosome 13q12-13
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Cited by
Inhibition of Poly(ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Fong, P. C., Boss, D. S., Yap, T. A., Tutt, A., Wu, P., Mergui-Roelvink, M., Mortimer, P., Swaisland, H., Lau, A., O'Connor, M. J., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0900212 · Cited by 3,634
Audeh, M. W., Carmichael, J., Penson, R. T., Friedlander, M., Powell, B., Bell-McGuinn, K. M., Scott, C., Weitzel, J. N., Oaknin, A., Loman, N., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60893-8 · Cited by 2,279
Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer
Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., Scott, C., Meier, W., Shapira-Frommer, R., Safra, T., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105535 · Cited by 1,883
ARID1A Mutations in Endometriosis-Associated Ovarian Carcinomas
Wiegand, K. C., Shah, S. P., Al-Agha, O. M., Zhao, Y., Tse, K., Zeng, T., Senz, J., McConechy, M. K., Anglesio, M. S., Kalloger, S. E., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1008433 · Cited by 1,712
Self-citationLedermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., Scott, C. L., Meier, W., Shapira-Frommer, R., Safra, T., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(14)70228-1 · Cited by 1,442
Metadata
- Authors
- Press, J. Z., De Luca, A., Boyd, N., Young, S., Troussard, A., Ridge, Y., Kaurah, P., Kalloger, S. E., Blood, K. A., Smith, M., Spellman, P. T., Wang, Y., Miller, D. M., Horsman, D., Faham, M., Gilks, C. B., Gray, J., & Huntsman, D. G.
- Venue
- BMC Cancer
- Published
- 2008-01-22
- Volume
- 8
- Issue
- 1
- Pages
- 17-17
- ISSN
- 1471-2407 (ISSN-L)
- OpenAlex
- W2112788544
- Cited by
- 287
- References
- 69
- FWCI
- 17.75
- Type
- journal article
- Language
- en
- Open access
- gold
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- Press, J. Z., De Luca, A., Boyd, N., Young, S., Troussard, A., Ridge, Y., Kaurah, P., Kalloger, S. E., Blood, K. A., Smith, M., Spellman, P. T., Wang, Y., Miller, D. M., Horsman, D., Faham, M., Gilks, C. B., Gray, J., & Huntsman, D. G. (2008). Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities. BMC Cancer. https://doi.org/10.1186/1471-2407-8-17
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