Evaluation of a 1021-gene NGS panel for HRD detection in clinical samples.

Abstract

e17569 Background: Molecular profiling of tumors using Next Generation Sequencing (NGS) enables the detection of genetic alterations associated with response to targeted therapies, as well as the assessment of genomic scars indicative of homologous recombination deficiency (HRD). HRD serves as a critical biomarker for predicting response to PARP inhibitors. In this study, the efficiency of a 1021-gene NGS panel was evaluated for HRD status analysis in comparison with validated methodologies in ovarian cancer tissues. Methods: A total of 43 tumor samples from 34 patients with known HRD status, based on validated Myriad and OncoScan methodologies, were analyzed. The NGS-based analysis (Gene+) included sequencing of 1021 genes and evaluation of genomic instability. Genomic instability was assessed using three key biological parameters: LOH (Loss of Heterozygosity), TAI (Telomeric Allelic Imbalance), and LST (Large-Scale Transitions). Key evaluation criteria included HRD score concordance, BRCA1/2 mutation detection, and methodology reproducibility. Results: HRD status showed a concordance rate of 97.1% (33/34) between the 1021+HRD panel and the validated Myriad test (Table 1). Discrepancies were observed in one sample, with an HRD score of 43 based on the 1021-gene panel, compared to 35 (Myriad), suggesting potential differences near the cutoff threshold. Sensitivity for BRCA1/2 mutation detection was 100%. Additionally, reproducibility of HRD detection was 100% across 12 repeated samples. Positive HRD scores remained consistent even at low TCC levels (≥20%), with an agreement rate of 95.7% (22/23). Conclusions: The new NGS methodology demonstrated high concordance with validated methodologies for HRD detection, robust BRCA mutation identification, and excellent reproducibility. These findings support its clinical utility for guiding therapeutic decisions with PARP inhibitors. Concordance between the validated NGS method and the 1021-gene pPanel. Validated HRD Test HRD + HRD - PPV NPV OPA r 1021+HRD HRD + 24 1 96.00% 100% 97.06% 0.9295 HRD - 0 9 p< .00001