Multicenter Evaluation of Decentralized Homologous Recombination Deficiency Testing for Enhanced Molecular Diagnosis of Ovarian Cancer
Year: 2026
Type: article
Abstract: Assessment of homologous recombination deficiency (HRD) and tumor BRCA1/2 mutation status in high-grade serous ovarian carcinoma (HGSOC) is clinically relevant for treatment decisions and for identifying tumors that may benefit from poly(adenosine diphosphate–ribose) polymerase inhibitors. The Myriad MyChoice® CDx HRD (M-HRD) assay is an established clinically validated HRD testing platform that is performed as a send-out test. We conducted a multicenter pilot study to assess the analytical feasibility and interlaboratory agreement of decentralized testing using the SOPHiA DDM™ Dx HRD Solution (SG-HRD). Three hospitals each contributed eight clinical HGSOC samples previously tested with M-HRD or with SG-HRD in a send-out platform. All centers independently prepared SG-HRD libraries and sequenced the complete set of 24 samples. Agreement with M-HRD was evaluated separately from comparisons with previous SG-HRD send-out results. Among specimens with interpretable M-HRD, overall percent agreement with local SG-HRD results was 95.0% (19/20), 90.0% (18/20), and 88.9% (16/18) at the three hospitals. BRCA1/2 variant calls were concordant with previous testing. Overall, the comparison with previous analyses by Myriad genetics or with previous SOPHiA GENETICS send-out results showed a high level of agreement, with discordances mainly observed in samples with values close to the classification threshold. The small, selected cohort, limited clinical replication, and absence of treatment-outcome assessment restrict precision estimates, generalizability, and conclusions regarding clinical validity. These findings support the analytical feasibility of decentralized SG-HRD testing, but larger studies are needed to characterize performance across a broader range of specimens and testing conditions.
Institutions: Instituto de Salud Carlos III, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red de Cáncer, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W7225631038