{"paper_id":"23ce98c0-abb4-4c9f-8ec5-1ffcb4e1956a","body_text":"Decoding HRD: A Genomic LOH-Based Assay Associated With Platinum Response and Survival in High-Grade Serous Ovarian Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Decoding HRD: A Genomic LOH-Based Assay Associated With Platinum Response and Survival in High-Grade Serous Ovarian Cancer Yi-Hsuan Lucy Lai, Peining Yu, Hsiao-Yun Lu, Kuan-Ying Chen, Kun-Lin Li, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9243705/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Homologous recombination deficiency (HRD) is a clinically relevant biomarker associated with therapeutic response to platinum-based chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors in high-grade serous ovarian cancer (HGSOC). We evaluated an NGS-based HRD assay integrating BRCA1/2 mutation detection with genomic loss of heterozygosity (gLOH) using 90 HGSOC tumor samples from the Friends of Cancer Research HRD Harmonization clinical cohort. HRD positivity was defined as pathogenic BRCA1/2 alterations and/or gLOH ≥ 0.4. Integrated HRD assessment classified 70% of tumors as HRD-positive and demonstrated improved prediction of platinum response compared with BRCA mutation status alone, including in tumors with low inter-assay consensus. Notably, a substantial proportion of platinum responders were identified among BRCA–wild-type tumors, including the majority of super-responders. HRD-positive status was associated with longer relapse-free survival and overall survival, whereas BRCA1/2 mutation status alone was not significantly associated with either outcome. These findings support BRCA/gLOH-integrated HRD assessment as a clinically relevant approach for identifying platinum-sensitive HGSOC and suggest its potential value in ovarian cancer patient stratification, particularly among BRCA–wild-type tumors. homologous recombination deficiency (HRD) PARP inhibitor genomic loss of heterozygosity (gLOH) BRCA1/2 high-grade serous ovarian cancer platinum response Full Text Additional Declarations Competing interest reported. Some authors are employees of ACT Genomics Co., Ltd., which developed the ACTHRD assay evaluated in this study. The authors declare no other competing financial or non-financial interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-9243705\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":618292931,\"identity\":\"1193c47c-a84f-49fc-9c09-fc7e7270923d\",\"order_by\":0,\"name\":\"Yi-Hsuan Lucy Lai\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yi-Hsuan\",\"middleName\":\"Lucy\",\"lastName\":\"Lai\",\"suffix\":\"\"},{\"id\":618292932,\"identity\":\"724df8a2-8333-4502-828f-9fbe7da3db69\",\"order_by\":1,\"name\":\"Peining Yu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Peining\",\"middleName\":\"\",\"lastName\":\"Yu\",\"suffix\":\"\"},{\"id\":618292933,\"identity\":\"71babfb9-8d10-4883-b9a8-16a13067d31b\",\"order_by\":2,\"name\":\"Hsiao-Yun Lu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hsiao-Yun\",\"middleName\":\"\",\"lastName\":\"Lu\",\"suffix\":\"\"},{\"id\":618292934,\"identity\":\"3d5f1ae7-f913-442d-8255-4b89e5bf961c\",\"order_by\":3,\"name\":\"Kuan-Ying Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kuan-Ying\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":618292935,\"identity\":\"fc9f0008-9e1e-4b20-99fb-e3039770fa16\",\"order_by\":4,\"name\":\"Kun-Lin Li\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Kun-Lin\",\"middleName\":\"\",\"lastName\":\"Li\",\"suffix\":\"\"},{\"id\":618292936,\"identity\":\"e29e9891-2c5f-4a72-abba-28f4b55368c8\",\"order_by\":5,\"name\":\"Hang-Che Yang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hang-Che\",\"middleName\":\"\",\"lastName\":\"Yang\",\"suffix\":\"\"},{\"id\":618292937,\"identity\":\"696afd35-655a-4bc3-9b8c-695d0e052178\",\"order_by\":6,\"name\":\"Shu-Jen Chen\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Shu-Jen\",\"middleName\":\"\",\"lastName\":\"Chen\",\"suffix\":\"\"},{\"id\":618292938,\"identity\":\"804e7d94-73d4-4a07-aceb-f1b27365045a\",\"order_by\":7,\"name\":\"Rachel Yi-Chen Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Rachel\",\"middleName\":\"Yi-Chen\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":618292939,\"identity\":\"85e7af2a-c598-4215-b94d-1e6508f7f7c8\",\"order_by\":8,\"name\":\"Dhruva Dave\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Alabama at Birmingham\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Dhruva\",\"middleName\":\"\",\"lastName\":\"Dave\",\"suffix\":\"\"},{\"id\":618292940,\"identity\":\"1186de66-9dee-4557-b630-4fd18655f1ed\",\"order_by\":9,\"name\":\"Rebecca C. Arend\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Alabama at Birmingham\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Rebecca\",\"middleName\":\"C.\",\"lastName\":\"Arend\",\"suffix\":\"\"},{\"id\":618292941,\"identity\":\"9662d0ef-a358-4d2d-8b92-eaa8ad1cab3a\",\"order_by\":10,\"name\":\"Prerana Bhan\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Prerana\",\"middleName\":\"\",\"lastName\":\"Bhan\",\"suffix\":\"\"},{\"id\":618292942,\"identity\":\"71990765-e41d-4ce0-8ced-8ec14e706041\",\"order_by\":11,\"name\":\"Yen-Jung Lu\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYFCCww0MH+AcA6K0HGxgnMHAIEGKFsYGZh64FmKAwcGDbdI2NXZ18u69Bx/dKLCzZ2A/fHQDXi0HgFpyjiVLGJ45l2ycY5Cc2MCTlnaDsBa2AxKGM3LMpHMMDiQwSPCYEdZi8Q+oZf4bsBZ74rQwth2QkAeqBGlhbCCkRfLAwWbL3r5kyQ08OcZgv7QR8gvfjcMHb/z4Zscv337G8HHOHzt7fvbDx/BqUbhxAOZCqAgbPuUgIN/fAGU0EFI6CkbBKBgFIxYAAA/YTAg/xuGyAAAAAElFTkSuQmCC\",\"orcid\":\"\",\"institution\":\"ACT Genomics Co., Ltd.\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Yen-Jung\",\"middleName\":\"\",\"lastName\":\"Lu\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2026-03-27 10:41:58\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-9243705/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-9243705/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":107869499,\"identity\":\"bfb245e9-59c3-4d3a-9253-98ea642d602a\",\"added_by\":\"auto\",\"created_at\":\"2026-04-27 07:37:11\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":847552,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"DecodingHRDManuscriptJOR2026030Final.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-9243705/v1_covered_bfb06476-ca2a-4806-8a57-452a09e1f7a3.pdf\"}],\"financialInterests\":\"Competing interest reported. Some authors are employees of ACT Genomics Co., Ltd., which developed the ACTHRD assay evaluated in this study. The authors declare no other competing financial or non-financial interests.\",\"formattedTitle\":\"Decoding HRD: A Genomic LOH-Based Assay Associated With Platinum Response and Survival in High-Grade Serous Ovarian Cancer\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"homologous recombination deficiency (HRD), PARP inhibitor, genomic loss of heterozygosity (gLOH), BRCA1/2, high-grade serous ovarian cancer, platinum response\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-9243705/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-9243705/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eHomologous recombination deficiency (HRD) is a clinically relevant biomarker associated with therapeutic response to platinum-based chemotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors in high-grade serous ovarian cancer (HGSOC). We evaluated an NGS-based HRD assay integrating \\u003cem\\u003eBRCA1/2\\u003c/em\\u003e mutation detection with genomic loss of heterozygosity (gLOH) using 90 HGSOC tumor samples from the Friends of Cancer Research HRD Harmonization clinical cohort. HRD positivity was defined as pathogenic \\u003cem\\u003eBRCA1/2\\u003c/em\\u003e alterations and/or gLOH\\u0026thinsp;\\u0026ge;\\u0026thinsp;0.4. Integrated HRD assessment classified 70% of tumors as HRD-positive and demonstrated improved prediction of platinum response compared with \\u003cem\\u003eBRCA\\u003c/em\\u003e mutation status alone, including in tumors with low inter-assay consensus. Notably, a substantial proportion of platinum responders were identified among BRCA\\u0026ndash;wild-type tumors, including the majority of super-responders. HRD-positive status was associated with longer relapse-free survival and overall survival, whereas \\u003cem\\u003eBRCA1/2\\u003c/em\\u003e mutation status alone was not significantly associated with either outcome. These findings support BRCA/gLOH-integrated HRD assessment as a clinically relevant approach for identifying platinum-sensitive HGSOC and suggest its potential value in ovarian cancer patient stratification, particularly among BRCA\\u0026ndash;wild-type tumors.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Decoding HRD: A Genomic LOH-Based Assay Associated With Platinum Response and Survival in High-Grade Serous Ovarian Cancer\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-04-07 19:23:04\",\"doi\":\"10.21203/rs.3.rs-9243705/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"e65fbaf4-b927-4687-8ab8-75300f1f17e6\",\"owner\":[],\"postedDate\":\"April 7th, 2026\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-04-25T11:55:05+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-04-07 19:23:04\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-9243705\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-9243705\",\"identity\":\"rs-9243705\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}