ArticleBMC cancer2013
BRCA1 promoter hypermethylation, 53BP1 protein expression and PARP-1 activity as biomarkers of DNA repair deficit in breast cancer.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Association of BRCA1 promoter methylation with sporadic breast cancers: Evidence from 40 studies.Scientific reports · 2015Pooled it
- Olaparib in HR-deficient, metastatic triple-negative breast and platinum-sensitive relapsed ovarian cancers without germline mutations in BRCA1/2: phase 2 EMBRACE trial.British journal of cancer · 2026Trial
- Higher Levels ofMedical sciences (Basel, Switzerland) · 2026Article
- Review
- BRCA promoter methylation in triple-negative breast cancer is preserved in xenograft models and represents a potential therapeutic marker for PARP inhibitors.Breast cancer research and treatment · 2025Article
- BRCA1 & BRCA2 methylation as a prognostic and predictive biomarker in cancer: Implementation in liquid biopsy in the era of precision medicine.Clinical epigenetics · 2024Review
- In Silico Mixed Ligand/Structure-Based Design of New CDK-1/PARP-1 Dual Inhibitors as Anti-Breast Cancer Agents.International journal of molecular sciences · 2023Article
- Review
- Targeting DNA repair for cancer treatment: Lessons from PARP inhibitor trials.Oncology research · 2023Review
- Review
- BRCA mutations lead to XIAP overexpression and sensitise ovarian cancer to inhibitor of apoptosis (IAP) family inhibitors.British journal of cancer · 2022Article
- The Clinical and Pathological Profile of BRCA1 Gene Methylated Breast Cancer Women: A Meta-Analysis.Cancers · 2021Review
- Clinicopathological Correlates of γδ T Cell Infiltration in Triple-Negative Breast Cancer.Cancers · 2021Article
- PRMT5 promotes DNA repair through methylation of 53BP1 and is regulated by Src-mediated phosphorylation.Communications biology · 2020Article
- Up-Regulation of PARP1 Expression Significantly Correlated with Poor Survival in Mucosal Melanomas.Cells · 2020Article
- Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders.The oncologist · 2020Review
- Article
- Constitutional Mosaic Epimutations - a hidden cause of cancer?Cell stress · 2019Review
- Increased single-strand annealing rather than non-homologous end-joining predicts hereditary ovarian carcinoma.Oncotarget · 2017Article
- Comprehensive Analysis of Cancer-Proteogenome to Identify Biomarkers for the Early Diagnosis and Prognosis of Cancer.Proteomes · 2017Review
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPoly(adenosine diphosphate-ribose) polymerase 1 (PARP-1) and the balance between BRCA1 and 53BP1 play a key role in the DNA repair and cell stress response. PARP inhibitors show promising clinical activity in metastatic triple negative (TN) or BRCA-mutated breast cancer. However, a comprehensive analysis of PARP-1 activity, BRCA1 promoter methylation and 53BP1 expression in tumours without known BRCA1 mutation has not yet been carried out.
methodsWe investigated cytosolic PARP-1 activity, 53BP1 protein levels and BRCA1 promoter methylation in 155 surgical breast tumour samples from patients without familial breast cancer history or known BRCA1 mutations who were treated between January 2006 and November 2009 and evaluated their statistical association with classical predictive and prognostic factors.
resultsThe mitotic count score was the only parameter clearly associated with PARP-1 activity. BRCA1 promoter hypermethylation (15.4% of all cancers) was significantly associated with uPA and PAI-1 levels, tumour grade, mitotic count score, hormone receptor and HER2 negative status and TN profile (29% of TN tumours showed BRCA1 promoter hypermethylation compared to 5% of grade II-III hormone receptor-positive/HER2-negative and 2% of HER2-positive tumours). No statistical association was found between BRCA1 promoter hypermethylation and PARP-1 activity. High 53BP1 protein levels correlated with lymph node positivity, hormone receptor positivity, molecular grouping, unmethylated BRCA1 promoter and PARP-1 activity. In TN tumours, BRCA1 promoter methylation was only marginally associated with age, PARP-1 activity was not associated with any of the tested clinico-pathological factors and high 53BP1 protein levels were significantly associated with lymph node positivity. Only 3 of the 14 TN tumours with BRCA1 promoter hypermethylation presented high 53BP1 protein levels.
conclusionsBreast cancers that harbour simultaneously high 53BP1 protein level and BRCA1 promoter hypermethylation and are the putative target population of drugs targeting DNA repair appear to be restricted to a small subgroup of TN tumours.
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