Abstract |
The genetic changes underlying in the development and progression of familial breast cancer are poorly understood. To identify a somatic genetic signature of tumor progression for each familial group, BRCA1, BRCA2, and non-BRCA1/BRCA2 (BRCAX) tumors, by high-resolution comparative genomic hybridization, we have analyzed 77 tumors previously characterized for BRCA1 and BRCA2 germ line mutations. Based on a combination of the somatic genetic changes observed at the six most different chromosomal regions and the status of the estrogen receptor, we developed using random forests a molecular classifier, which assigns to a given tumor a probability to belong either to the BRCA1 or to the BRCA2 class. Because 76.5% (26 of 34) of the BRCAX cases were classified with our predictor to the BRCA1 class with a probability of >50%, we analyzed the BRCA1 promoter region for aberrant methylation in all the BRCAX cases. We found that 15 of the 34 BRCAX analyzed tumors had hypermethylation of the BRCA1 gene. When we considered the predictor, we observed that all the cases with this epigenetic event were assigned to the BRCA1 class with a probability of >50%. Interestingly, 84.6% of the cases (11 of 13) assigned to the BRCA1 class with a probability >80% had an aberrant methylation of the BRCA1 promoter. This fact suggests that somatic BRCA1 inactivation could modify the profile of tumor progression in most of the BRCAX cases.
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Authors | Sara Alvarez, Ramon Diaz-Uriarte, Ana Osorio, Alicia Barroso, Lorenzo Melchor, Maria Fe Paz, Emiliano Honrado, Raquel Rodríguez, Miguel Urioste, Laura Valle, Orland Díez, Juan Cruz Cigudosa, Joaquin Dopazo, Manel Esteller, Javier Benitez |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 11
Issue 3
Pg. 1146-53
(Feb 01 2005)
ISSN: 1078-0432 [Print] United States |
PMID | 15709182
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BRCA1 Protein
- BRCA2 Protein
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Topics |
- BRCA1 Protein
(genetics)
- BRCA2 Protein
(genetics)
- Breast Neoplasms
(genetics, pathology)
- Chromosomes, Human, Pair 12
(genetics)
- Chromosomes, Human, Pair 15
(genetics)
- Chromosomes, Human, Pair 18
(genetics)
- Chromosomes, Human, Pair 2
(genetics)
- Chromosomes, Human, Pair 8
(genetics)
- DNA Methylation
- Female
- Genome, Human
- Humans
- Male
- Mutation
- Nucleic Acid Hybridization
(methods)
- Promoter Regions, Genetic
(genetics)
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