{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:10:16Z","timestamp":1785409816209,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HR22C1832"],"award-info":[{"award-number":["HR22C1832"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HR22C1832"],"award-info":[{"award-number":["HR22C1832"]}],"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004600","name":"Kyungpook National University Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004600","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/04qn0xg47","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Homologous recombination deficiency (HRD) is emerging as a clinically relevant biomarker across diverse tumor types, in addition to ovarian cancer. In this study, we evaluated the genomic instability score (GIS) across multiple tumor types using the TruSight Oncology 500 HRD assay, which incorporates the Myriad Genetics GIS algorithm, a widely used reference standard for HRD assessment. Methods: A total of 162 tumor samples (17 ovarian cancers and 145 non-ovarian tumors) underwent next-generation sequencing using the TruSight Oncology 500 HRD assay. Results: A total of 14 tumors were classified as GIS-High, defined as a GIS score \u226542, representing 8.6% of all cases. Among ovarian cancers, 7 out of 17 cases (41.2%) met the GIS-High threshold. Among non-ovarian tumors, seven GIS-High tumors were identified, accounting for 4.8% of cases (7\/145). GIS-High cases occurred in breast (n = 4), lung (n = 2), and hepatobiliary tract (n = 1) cancers. GIS scores showed significant associations with BRCA1\/2 and TP53 mutational status. In contrast, alterations in HRD-related genes other than BRCA1\/2 did not show significant associations with GIS score. Conclusions: GIS-High tumors were identified in a small subset of non-ovarian cancers. These findings support further investigation of GIS as an exploratory biomarker of HRD-like genomic scarring beyond ovarian cancer, but its predictive and therapeutic relevance in non-ovarian tumors requires additional validation.<\/jats:p>","DOI":"10.3390\/diagnostics16121802","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T12:14:58Z","timestamp":1781180098000},"page":"1802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Instability Score Across Diverse Tumor Types Using the Illumina TruSight Oncology 500 HRD Assay"],"prefix":"10.3390","volume":"16","author":[{"given":"Moonsik","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An Na","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora Jee-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghilsuk","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7571-1064","authenticated-orcid":false,"given":"Ji Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s41576-021-00338-8","article-title":"Clinical cancer genomic profiling","volume":"22","author":"Chakravarty","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrg2841","article-title":"Advances in understanding cancer genomes through second-generation sequencing","volume":"11","author":"Meyerson","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41571-024-00932-9","article-title":"Tumour mutational burden: Clinical utility, challenges and emerging improvements","volume":"21","author":"Budczies","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/cam4.1372","article-title":"Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients","volume":"7","author":"Vanderwalde","year":"2018","journal-title":"Cancer Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.modpat.2022.100049","article-title":"Homologous Recombination Repair Deficiency: An Overview for Pathologists","volume":"36","author":"Doig","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1093\/bioinformatics\/btac122","article-title":"SEPA: Signaling entropy-based algorithm to evaluate personalized pathway activation for survival analysis on pan-cancer data","volume":"38","author":"Li","year":"2022","journal-title":"Bioinformatics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108703","DOI":"10.1016\/j.compbiolchem.2025.108703","article-title":"Microbiome-transcriptome-histology triad enhances survival risk stratification in multiple cancers","volume":"120","author":"He","year":"2026","journal-title":"Comput. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41571-018-0114-z","article-title":"State-of-the-art strategies for targeting the DNA damage response in cancer","volume":"16","author":"Tang","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"975","DOI":"10.4143\/crt.2024.154","article-title":"Recent Advances in Genomic Approaches for the Detection of Homologous Recombination Deficiency","volume":"56","author":"Kim","year":"2024","journal-title":"Cancer Res. Treat."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1056\/NEJMe0903044","article-title":"Synthetic lethality\u2014A new direction in cancer-drug development","volume":"361","author":"Iglehart","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/genetics\/31.3.269","article-title":"Genetics of natural populations; recombination and variability in populations of Drosophila pseudoobscura","volume":"31","author":"Dobzhansky","year":"1946","journal-title":"Genetics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1038\/bjc.2012.451","article-title":"Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer","volume":"107","author":"Abkevich","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1158\/2159-8290.CD-11-0206","article-title":"Telomeric allelic imbalance indicates defective DNA repair and sensitivity to DNA-damaging agents","volume":"2","author":"Birkbak","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5454","DOI":"10.1158\/0008-5472.CAN-12-1470","article-title":"Ploidy and large-scale genomic instability consistently identify basal-like breast carcinomas with BRCA1\/2 inactivation","volume":"72","author":"Popova","year":"2012","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"288","DOI":"10.32074\/1591-951X-791","article-title":"In-house testing for homologous recombination repair deficiency (HRD) testing in ovarian carcinoma: A feasibility study comparing AmoyDx HRD Focus panel with Myriad myChoiceCDx assay","volume":"114","author":"Fumagalli","year":"2022","journal-title":"Pathologica"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/ijc.35457","article-title":"Limited association between HRR gene alterations and HRD in molecular tumor board cancer samples: Who should be tested for HRD?","volume":"157","author":"Schubart","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40364-025-00740-y","article-title":"Homologous recombination deficiency (HRD) testing landscape: Clinical applications and technical validation for routine diagnostics","volume":"13","author":"Witz","year":"2025","journal-title":"Biomark. Res."},{"key":"ref_19","unstructured":"U.S. Food and Drug Administration (2018). PD-L1 IHC 22C3 pharmDx SK006 50 Tests for Use with Autostainer Link 48."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0140-6736(21)00797-2","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial","volume":"398","author":"Janjigian","year":"2021","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jmoldx.2016.10.002","article-title":"Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists","volume":"19","author":"Li","year":"2017","journal-title":"J. Mol. Diagn."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1158\/2159-8290.CD-15-0714","article-title":"Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer","volume":"5","author":"Konstantinopoulos","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Yamamoto, H., and Hirasawa, A. (2021). Homologous Recombination Deficiencies and Hereditary Tumors. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010348"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41586-020-1943-3","article-title":"The repertoire of mutational signatures in human cancer","volume":"578","author":"Alexandrov","year":"2020","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wen, H., Feng, Z., Ma, Y., Liu, R., Ou, Q., Guo, Q., Shen, Y., Wu, X., Shao, Y., and Bao, H. (2022). Homologous recombination deficiency in diverse cancer types and its correlation with platinum chemotherapy efficiency in ovarian cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09602-4"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S385","DOI":"10.1016\/j.annonc.2021.08.347","article-title":"67P Homologous recombination deficiency in diverse cancer types and its correlation with platinum chemotherapy efficiency in ovarian cancer","volume":"32","author":"Wen","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/s41586-022-04738-6","article-title":"Signatures of copy number alterations in human cancer","volume":"606","author":"Steele","year":"2022","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1038\/s41467-018-04492-2","article-title":"Whole-genome sequencing reveals genomic signatures associated with the inflammatory microenvironments in Chinese NSCLC patients","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1093\/nar\/gky1142","article-title":"Sources of erroneous sequences and artifact chimeric reads in next generation sequencing of genomic DNA from formalin-fixed paraffin-embedded samples","volume":"47","author":"Haile","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"bbaf580","DOI":"10.1093\/bib\/bbaf580","article-title":"Deep learning-based fusion of nuclear segmentation features for microsatellite instability and tumor mutational burden prediction in digestive tract cancers: A multicenter validation study","volume":"26","author":"Zhang","year":"2025","journal-title":"Brief. Bioinform."},{"key":"ref_31","first-page":"1","article-title":"Homologous Recombination Deficiency in Breast Cancer: A Clinical Review","volume":"1","author":"Schrader","year":"2017","journal-title":"JCO Precis. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1002\/gcc.22921","article-title":"Homologous recombination deficiency in breast cancer: Implications for risk, cancer development, and therapy","volume":"60","author":"Ali","year":"2021","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.36922\/arnm.4557","article-title":"Different diagnostic methods for biliary tract cancer: A review","volume":"3","author":"Yakub","year":"2025","journal-title":"Adv. Radiother. Nucl. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1056\/NEJMoa1910962","article-title":"Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer","volume":"381","author":"Pothuri","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2416","DOI":"10.1056\/NEJMoa1911361","article-title":"Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer","volume":"381","author":"Pautier","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41568-020-0262-1","article-title":"p53: 800 million years of evolution and 40 years of discovery","volume":"20","author":"Levine","year":"2020","journal-title":"Nat. Rev. Cancer"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/12\/1802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:28:43Z","timestamp":1781324923000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/12\/1802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,11]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["diagnostics16121802"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16121802","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,11]]}}}