Assessment of genomic instability and homologous recombination repair in ovarian cancer using the Oncomine Comprehensive Assay Plus

Isabell Goetting1, Achim Rau1, Luisa Russ2, Stefan Kommoss2,5, Marcel Grube2,5, Tobias Engler2, Sara Brucker2, Carsten Denkert3, Franziska Mihalik1, Philip Jermann4, Cecília Durães4, Ute Kusch4, Andreas Hartkopf2, Falko Fend1, Annette Staebler1 and Irina Bonzheim1 1 Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen, Eberhard-Karls-University, Liebermeisterstraße 8, Tübingen 72076, Germany 2 Department of Woman’s Health, Eberhard-Karls-University, Tübingen, Germany 3 Institute of Pathology, Philipps University Marburg, Marburg University Hospital (UKGM), and University Cancer Center Frankfurt-Marburg (UCT), Marburg, Germany 4 Thermo Fisher Scientific, Waltham, MA 02451, USA 5 Current affiliation completion after the study: Department of Obstetrics and Gynecology, Schwaebisch Hall 74523, Germany Correspondence to: Annette Staebler, email:[email protected] Keywords: HRD assessment; ovarian cancer; BRCA; genomic instability; homologous recombination repair Received: August 29, 2025 Accepted: October 20, 2026 Published: November 05, 2026 Copyright: © 2026 Goetting et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Homologous recombination deficiency (HRD) is associated with response to poly (ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer and can be assessed through BRCA1/2 loss-of-function alterations and overall genomic instability. HRD status was characterized in 58 ovarian cancer samples, primarily high-grade serous ovarian carcinoma (HGSC, n = 52), using the Oncomine™ Comprehensive Assay (OCA) Plus. HRD status was determined based on BRCA1/2 variants and a genomic instability metric (GIM) and compared with the FDA-approved gold standard method MyChoice® CDx assay. Overall, 33 samples (56.9%) were HRD-positive, including 53.4% of HGSC samples. BRCA1/2 mutations were detected in 11 samples (19.0%), with BRCA1 more frequently affected. Concordance between OCA Plus and MyChoice CDx assays was 91.4% for BRCA1/2 alterations, 83.3% for GIM, and 86.0% for HRD classification. Additional alterations of potential clinical relevance such as variants in homologous recombination repair genes, including ATM, PTEN, FANCE, and CDK12, CCNE1 amplifications, and TP53 mutations (86.2%) were detected. Loss of heterozygosity in BRCA1/2-mutated samples suggested potential biallelic loss-of-function. HRD-positive tumors, including both BRCA1/2-mutated and BRCA-wild type cases, showed significantly longer recurrence-free survival and apparent clinical benefit from PARPi treatment. This study supports the feasibility of in-house HRD assessment using comprehensive genomic profiling panels for precise molecular characterization.