Background: Homologous recombination repair (HRR) is the main mechanism of repair of DNA double-strand breaks. Its deficiency (HRD) is a common feature of epithelial ovarian cancers (EOCs). BRCA1/2 mutations and/or other aberrations in genes of HRR are well known causes of HRD and genomic instability. Poly ADP-ribose polymerase inhibitors (PARPi) have revolutionized the management of BRCA mutant EOCs and demonstrated activity in HRD tumor cells. Determining HRD status can provide informations on the magnitude of benefit for PARPi therapy. Myriad MyChoice CDx is a next generation sequencing- based in vitro diagnostic test that assesses the Genomic Instability Score (GIS) which is an algorithmic measurement of loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. However Myriad MyChoice CDx, is a centrally performed and costly assay, with no reimbursement scheduled, at least in Italy.
Methods: In this report, we described our experience in performing the HRD Focus AmoyDx (Amoy Diagnostics Ltd, Xiamen, Fujian, China) on the same samples of EOCs evaluated with Myriad MyChoiceCDx assay.
Results: The overall percent agreement between AmoyDx and Myriad was 87.8% (65 of 74 tumors tested). All the 36 AmoyDx negative cases were confirmed to be negative by Myriad (negative predictive value, 100%).
Conclusions: The concordance of the results with the gold standard Myriad MyChoice CDx assay suggest the feasibility and reliability of HRD testing in diagnostic laboratories with high-throughput NGS platforms and qualified personnel.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624133 | PMC |
| http://dx.doi.org/10.32074/1591-951X-791 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
RAD51 testing in patients with early HER2-negative breast cancer and homologous recombination deficiency: post-hoc analysis of the GeparOla trial.
Clin Cancer Res
December 2024
Vall d'Hebron Institute of Oncology, Barcelona, Spain.
Purpose: The randomized GeparOla trial reported comparable pathological complete response (pCR) rates with neoadjuvant containing olaparib vs. carboplatin treatment. Here, we evaluate the association between functional homologous repair deficiency (HRD) by RAD51 foci and pCR, and the potential of improving patient selection by combining RAD51 and stromal tumor infiltrating lymphocytes (sTILs).
View Article and Find Full Text PDFFactors associated with an inconclusive result from commercial homologous recombination deficiency testing in ovarian cancer.
Cancer
January 2025
Gynecologic Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Introduction: Homologous recombination deficiency (HRD) testing is used to determine the appropriateness of poly ADP-ribose polymerase inhibitors for patients with epithelial ovarian cancer and no germline/somatic BRCA1/2 alterations. Myriad MyChoice CDx reports a genomic instability score (GIS) to quantify the level of HRD, with a positive score defined as ≥42. The authors sought to define factors associated with obtaining an inconclusive HRD test result.
View Article and Find Full Text PDFHomologous recombination deficiency should be tested for in patients with advanced stage high-grade serous ovarian cancer aged 70 years and over.
Gynecol Oncol
August 2024
School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, NSW, Australia; Department of Medical Oncology, The Prince of Wales and Royal Hospital for Women, Randwick, NSW, Australia. Electronic address:
Objective: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group.
Methods: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®.
Olaparib Addition to Maintenance Bevacizumab Therapy in Ovarian Carcinoma With BRCA-Like Genomic Aberrations.
JAMA Netw Open
April 2024
Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology, Medical Faculty, University Hospital Cologne, Cologne, Germany.
Importance: Testing for homologous recombination deficiency is required for the optimal treatment of high-grade epithelial ovarian cancer. The search for accurate biomarkers is ongoing.
Objective: To investigate whether progression-free survival (PFS) and overall survival (OS) of patients with high-grade epithelial ovarian cancer treated with maintenance olaparib or placebo differed between patients with a tumor BRCA-like genomic profile and patients without a tumor BRCA-like profile.
High Concordance of Different Assays in the Determination of Homologous Recombination Deficiency-Associated Genomic Instability in Ovarian Cancer.
JCO Precis Oncol
March 2024
Institute of Pathology, School of Medicine and Health, Technical University Munich, Munich, Germany.
Article Synopsis
- PARP inhibitors have shown effectiveness in treating ovarian cancer, particularly benefiting patients with homologous recombination deficiency (HRD), and various assays can be used to assess these biomarkers.
- The study compares the performance of multiple molecular assays for genomic instability (GI) against the standard Myriad myChoice assay using DNA from high-grade serous ovarian cancer (HGSOC) samples.
- Results indicate high concordance between different assays for assessing GI, supporting their use in clinical settings for HRD evaluation, which aligns with European Medicines Agency guidelines for PARP inhibitor treatment.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!