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Rare copy number variants observed in hereditary breast cancer cases disrupt genes in estrogen signaling and TP53 tumor suppression network.
- Source :
-
PLoS genetics [PLoS Genet] 2012; Vol. 8 (6), pp. e1002734. Date of Electronic Publication: 2012 Jun 21. - Publication Year :
- 2012
-
Abstract
- Breast cancer is the most common cancer in women in developed countries, and the contribution of genetic susceptibility to breast cancer development has been well-recognized. However, a great proportion of these hereditary predisposing factors still remain unidentified. To examine the contribution of rare copy number variants (CNVs) in breast cancer predisposition, high-resolution genome-wide scans were performed on genomic DNA of 103 BRCA1, BRCA2, and PALB2 mutation negative familial breast cancer cases and 128 geographically matched healthy female controls; for replication an independent cohort of 75 similarly mutation negative young breast cancer patients was used. All observed rare variants were confirmed by independent methods. The studied breast cancer cases showed a consistent increase in the frequency of rare CNVs when compared to controls. Furthermore, the biological networks of the disrupted genes differed between the two groups. In familial cases the observed mutations disrupted genes, which were significantly overrepresented in cellular functions related to maintenance of genomic integrity, including DNA double-strand break repair (P = 0.0211). Biological network analysis in the two independent breast cancer cohorts showed that the disrupted genes were closely related to estrogen signaling and TP53 centered tumor suppressor network. These results suggest that rare CNVs represent an alternative source of genetic variation influencing hereditary risk for breast cancer.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Adult
Aged
Aged, 80 and over
BRCA1 Protein genetics
BRCA2 Protein genetics
Breast Neoplasms metabolism
Estrogens genetics
Fanconi Anemia Complementation Group N Protein
Female
Humans
Middle Aged
Mutation
Nuclear Proteins genetics
Signal Transduction
Tumor Suppressor Protein p53 genetics
Tumor Suppressor Proteins genetics
Breast Neoplasms genetics
DNA Copy Number Variations
Estrogens metabolism
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 8
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 22737080
- Full Text :
- https://doi.org/10.1371/journal.pgen.1002734