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Updated: Jul 13, 2026
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
[Mutation frequency of homologous recombination repair genes in prostate adenocarcinomas]
Zsombor Melegh1, Erzsébet Csernák1, Andrea Kohánka1
1Sebészeti és Molekuláris Patológiai Osztály, Országos Onkológiai Intézet, Budapest, Hungary. dr.toth.erika@oncol.hu.
Abstract:
The best predictive marker for the expected efficacy of PARP inhibitor therapy is mutations in BRCA1/2 or other homologous recombination repair genes. These tests are part of routine molecular pathology diagnostics. Among 281 patients with prostate adenocarcinoma, somatic pathogenic mutations in one of these genes were identified in 21.4% of patients. In 28.5% of the patients, the test was unsuccessful; the main limitation of successful testing was the age of the paraffin blocks and low DNA concentration. In the case of BRCA1/2 testing, the success rate was significantly reduced for samples older than 5 years, while in tests involving a broader set of homologous recombination repair genes, the success rate was significantly reduced for samples older than 2 years. Therefore, it is very important to test high-risk prostate cancers at the time of primary diagnosis, and probably also liquid biopsy testing of circulating tumor DNA will play an important role in safe diagnosis in the near future.
Insights
Somatic mutations in homologous recombination repair genes predict PARP inhibitor therapy efficacy in prostate cancer. Testing success is limited by sample age and DNA quality, highlighting the need for timely diagnosis.
Area of Science:
- Oncology
- Molecular Pathology
- Genetics
Context:
- PARP inhibitor therapy is a key treatment for prostate cancer.
- Predictive markers for treatment efficacy are crucial for personalized medicine.
- Homologous recombination repair (HRR) gene mutations are established biomarkers.
Purpose:
- To assess the prevalence of HRR gene mutations in prostate adenocarcinoma.
- To evaluate the success rate and limitations of molecular testing for these mutations.
- To emphasize the importance of early diagnosis and potential of liquid biopsies.
Summary:
- Somatic pathogenic mutations in BRCA1/2 or other HRR genes were found in 21.4% of 281 prostate adenocarcinoma patients.
- Testing success rates were impacted by paraffin block age and low DNA concentration, with older samples (>5 years for BRCA1/2, >2 years for broader HRR panels) showing reduced success.
- These findings underscore the importance of testing high-risk prostate cancers at initial diagnosis and suggest a future role for circulating tumor DNA liquid biopsies.
Impact:
- Identifies key predictive biomarkers for PARP inhibitor therapy in prostate cancer.
- Highlights critical pre-analytical factors affecting molecular diagnostic test success.
- Informs clinical practice regarding optimal timing for genetic testing and potential for novel diagnostic approaches like liquid biopsy.
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