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Updated: Jan 28, 2026
Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
Published on: February 17, 2011
Clinical importance of FANCD2, BRIP1, BRCA1, BRCA2 and FANCF expression in ovarian carcinomas
Joanna Moes-Sosnowska1, Iwona K Rzepecka2, Joanna Chodzynska3
1a Department of Immunology , Maria Sklodowska-Curie Institute - Oncology Center , Warsaw , Poland.
Objective:
DNA repair pathways are potential targets of molecular therapy in cancer patients. The FANCD2, BRIP1, BRCA1/2, and FANCF genes are involved in homologous recombination DNA repair, which implicates their possible role in cell response to DNA-damaging agents. We evaluated a clinical significance of pre-treatment expression of these genes at mRNA level in 99 primary, advanced-stage ovarian carcinomas from patients, who later received taxane-platinum (TP) or platinum-cyclophosphamide (PC) treatment.
Methods:
Gene expression was determined with the use of Real-Time PCR. The BRCA2 and BRIP1 gene sequence was investigated with the use of SSCP, dHPLC, and PCR-sequencing.
Results:
Increased FANCD2 expression occurred to be a negative prognostic factor for all patients (PC+TP:HR 3.85, p = 0.0003 for the risk of recurrence; HR 1.96, p = 0.02 for the risk of death), and this association was even stronger in the TP-treated group (HR 6.7, p = 0.0002 and HR 2.33, p = 0.01, respectively). Elevated BRIP1 expression was the only unfavorable molecular factor in the PC-treated patients (HR 8.37, p = 0.02 for the risk of recurrence). Additionally, an increased FANCD2 and BRCA1/2 expression levels were associated with poor ovarian cancer outcome in either TP53-positive or -negative subgroups of the TP-treated patients, however these groups were small. Sequence analysis identified one protein truncating variant (1/99) in BRCA2 and no mutations (0/56) in BRIP1.
Conclusions:
Our study shows for the first time that FANCD2 overexpression is a strong negative prognostic factor in ovarian cancer, particularly in patients treated with TP regimen. Moreover, increased mRNA level of the BRIP1 is a negative prognostic factor in the PC-treated patients. Next, changes in the BRCA2 and BRIP1 genes are rare and together with other analyzed FA genes considered as homologous recombination deficiency may not affect the expression level of analyzed genes.
Insights
High FANCD2 gene expression predicts poor outcomes in ovarian cancer patients, especially those treated with taxane-platinum (TP) chemotherapy. Increased BRIP1 gene expression is also linked to worse prognosis in platinum-cyclophosphamide (PC) treated patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- DNA repair pathways are crucial for cancer therapy.
- Homologous recombination (HR) DNA repair genes like FANCD2, BRIP1, BRCA1/2, and FANCF are implicated in cancer cell response to DNA-damaging agents.
- Understanding the role of these genes in ovarian cancer prognosis is vital for treatment stratification.
Purpose of the Study:
- To evaluate the clinical significance of pre-treatment mRNA expression of FANCD2, BRIP1, BRCA1/2, and FANCF in advanced-stage ovarian carcinomas.
- To determine the prognostic value of these genes in patients receiving taxane-platinum (TP) or platinum-cyclophosphamide (PC) chemotherapy.
Main Methods:
- Gene expression analysis using Real-Time PCR.
- Gene sequencing (SSCP, dHPLC, PCR-sequencing) for BRCA2 and BRIP1.
- Retrospective analysis of 99 advanced-stage ovarian cancer patients.
Main Results:
- Overexpression of FANCD2 was a significant negative prognostic factor for recurrence and death in all patients, particularly those treated with TP chemotherapy.
- Elevated BRIP1 expression was an unfavorable prognostic factor for recurrence in patients treated with PC chemotherapy.
- Increased FANCD2 and BRCA1/2 expression correlated with poor outcomes in TP53-positive and -negative subgroups of TP-treated patients.
Conclusions:
- FANCD2 overexpression is a strong negative prognostic indicator in ovarian cancer, especially with TP treatment.
- Increased BRIP1 mRNA levels indicate a poor prognosis for patients receiving PC treatment.
- Mutations in BRCA2 and BRIP1 are rare, suggesting that homologous recombination deficiency may not always manifest as altered expression of these specific genes.
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