A Benchmark of In-House Homologous Recombination Repair Deficiency Testing Solutions for High-Grade Serous Ovarian Cancer Diagnosis

Version 1 : Received: 17 July 2023 / Approved: 3 August 2023 / Online: 3 August 2023 (10:49:27 CEST)
Version 2 : Received: 28 August 2023 / Approved: 1 September 2023 / Online: 6 September 2023 (09:09:09 CEST)

A peer-reviewed article of this Preprint also exists.

Guarischi-Sousa, R.; Kroll, J.E.; Bonaldi, A.; Pierry, P.M.; Villela, D.; Souza, C.A.; Silva, J.S.; Bürger, M.C.; Oliveira, F.A.; de Paula, M.G.; Meliso, F.M.; de Almeida, L.G.; Monfredini, P.M.; de Oliveira, A.G.; Milanezi, F.; Scapulatempo-Neto, C.; Yamamoto, G.L. A Benchmark of In-House Homologous Recombination Repair Deficiency Testing Solutions for High-Grade Serous Ovarian Cancer Diagnosis. Diagnostics 2023, 13, 3293. Guarischi-Sousa, R.; Kroll, J.E.; Bonaldi, A.; Pierry, P.M.; Villela, D.; Souza, C.A.; Silva, J.S.; Bürger, M.C.; Oliveira, F.A.; de Paula, M.G.; Meliso, F.M.; de Almeida, L.G.; Monfredini, P.M.; de Oliveira, A.G.; Milanezi, F.; Scapulatempo-Neto, C.; Yamamoto, G.L. A Benchmark of In-House Homologous Recombination Repair Deficiency Testing Solutions for High-Grade Serous Ovarian Cancer Diagnosis. Diagnostics 2023, 13, 3293.

Abstract

Homologous recombination deficiency (HRD) has become an important prognostic and predictive biomarker for patients with high-grade serous ovarian cancer who may benefit from poly-ADP ribose polymerase inhibitors (PARPi) and platinum-based therapies. HRD testing provides relevant information to personalize patients’ treatment options, and it has been progressively incorporated in diagnostic laboratories. In this study, we evaluated the feasibility of in-house HRD testing deployable in a diagnostic clinical setting, comparing results from two commercially available next-generation sequencing (NGS)-based tumor tests (SOPHiA DDMTM HRD Solution and AmoyDx HRD Focus Panel) with the reference assay from Myriad MyChoice CDx. A total of 85 ovarian cancer samples were subjected to HRD testing. An overall strong correlation was observed across the three assays evaluated, regardless of the different underlying methods employed to assess genomic instability, with the highest pairwise correlation between Myriad and SOPHiA (R=0.87, p-value=3.39x10-19). The comparison of the assigned HRD status to the reference Myriad’s test revealed a positive predictive value (PPV) and negative predictive value (NPV) of 90.9% and 96.3% for SOPHiA’s test, while AmoyDx’s test achieved 75% PPV and 100% NPV. This is the largest HRD testing evaluation using different methodologies and provides a clear picture of the robustness of NGS-based tests currently offered in the market. Our data show that the implementation of in-house HRD testing in diagnostic laboratories is technically feasible and it can be reliably performed with commercial assays. Also, the turnaround time is compatible with clinical needs, being an ideal alternative to offer to a broader number of patients, while still maintaining high-quality standards at more accessible price tiers.

Keywords

homologous recombination deficiency (HRD); biomarkers; ovarian cancer; DNA repair; BRCA1/2; poly (ADP–ribose) polymerase inhibitors (PARPi); next generation sequencing (NGS)

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)

Comment 1

Received: 6 September 2023
Commenter: Rodrigo Guarischi-Sousa
Commenter's Conflict of Interests: Author

Comment: Correcting typo on author's name (Adriano Bonaldi); minor corrections to the manuscript

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