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BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.
- Source :
- Molecular Oncology; Oct2015, Vol. 9 Issue 8, p1528-1538, 11p
- Publication Year :
- 2015
-
Abstract
- Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10–15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1 -mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1 -like or non- BRCA1 -like. BRCA1 mutation, promoter methylation, BRCA1 -like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1 -like and non- BRCA1 -like tumors were compared. Multivariate survival analysis was performed using the Cox proportional hazards model. BRCA1 germline mutation was identified in 10% of patients and 15% of tumors were BRCA1 promoter methylated. Fifty-five percent of tumors classified as BRCA1 -like. The functions of genes significantly up-regulated in BRCA1 -like tumors included cell cycle and DNA recombination and repair. TP53 was found to be frequently mutated in BRCA1 -like ( P < 0.05), while PIK3CA was frequently mutated in non- BRCA1 -like tumors ( P < 0.05). A significant association with worse prognosis was evident for patients with BRCA1 -like tumors (adjusted HR = 3.32, 95% CI = 1.30–8.48, P = 0.01). TN tumors can be further divided into two major subgroups, BRCA1 -like and non- BRCA1 -like with different mutation and expression patterns and prognoses. Based on these molecular patterns, subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15747891
- Volume :
- 9
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Molecular Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 109884746
- Full Text :
- https://doi.org/10.1016/j.molonc.2015.04.011