{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:22:15Z","timestamp":1792214535652,"version":"4.4.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Along with <jats:italic>BRCA<\/jats:italic> mutation status, homologous recombination deficiency (HRD) testing is a prognostic and predictive biomarker for poly-ADP-ribose polymerase (PARP) inhibitor therapy indication in high-grade epithelial ovarian, fallopian tube, or peritoneal cancer. Approximately 50% of high-grade serous ovarian cancers exhibit HRD, even in the absence of germline or somatic <jats:italic>BRCA<\/jats:italic>1\/2 loss-of-function mutations. In this scenario, access to a validated diagnostic HRD test can optimize treatment selection and increase the effectiveness of the intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To technically validate an <jats:italic>in-house<\/jats:italic> next-generation sequencing (NGS)-based HRD test, QIAseq Custom Panel (QIAGEN), by comparing it with the reference assay, MyChoice CDx\u00ae Plus HRD (Myriad Genetics), which is used in routine care.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a prospective cohort study conducted at the Oncocl\u00ednicas Precision Medicine (OCPM) laboratory using samples from patients with advanced or relapsed platinum-sensitive ovarian cancer eligible for HRD testing in a diagnostic clinical setting at Oncocl\u00ednicas and Co. We assessed the performance of the in-house test (GS Focus HRD) using Cohen\u2019s kappa statistic to measure agreement with the gold standard assay (MyChoice\u00ae HRD Plus CDx) in HRD status classification, along with other accuracy metrics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 41 samples were analyzed (20 HRD-positive, 19 HRD-negative, and 2 inconclusive results with the MyChoice\u00ae HRD Plus CDx assay). The GS Focus HRD test demonstrated high concordance for HRD status with the reference test (kappa: 0.8 and 95% CI: 0.60\u20130.98). Overall accuracy, sensitivity, and specificity were 90%. Six samples had <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> mutations identified by the MyChoice\u00ae HRD Plus CDx, all of which were detected by the GS Focus HRD test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, the results demonstrate substantial agreement and high accuracy of the NGS-based GS Focus HRD test compared to MyChoice\u00ae HRD Plus CDx. Our in-house assay is eligible for diagnostic test approval and market access as per Brazilian regulations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmolb.2025.1524594","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:11:14Z","timestamp":1739250674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Homologous recombination deficiency test validation in patients with high-grade advanced ovarian cancer"],"prefix":"10.3389","volume":"12","author":[{"given":"Angelica","family":"Nogueira Rodrigues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreza Karine de Barros Almeida","family":"Souto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dioc\u00e9sio Alves Pinto","family":"de 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