Angelica Nogueira Rodrigues, Andreza Karine de Barros Almeida Souto, Diocésio Alves Pinto de Andrade, Larissa Müller Gomes, Sandra Satie Koide, Renata de Godoy E Silva, Bruno Batista de Souza, Juliana Doblas Massaro, Andréia Cristina de Melo, Andrea Morais Borges, Camila Giro, Carlos Augusto Vasconcelos de Andrade, Cesar Martins da Costa, Daniel Luiz Gimenes, Eduardo Caminha Bandeira de Mello, Fernanda Cesar de Oliveira, Frederico Müller de Toledo Lima, Gabriel Lima Lopes, Gustavo de Oliveira Bretas, Gustavo Guerra Jacob, Herika Lucia da Costa Silva, Juliana Ferrari Notaro, Lara Ladislau Alves, Marcos Veloso Moitinho, Mirian Cristina da Silva, Roberto Abramoff, Thais Amaral da Cunha Rauber, Rodrigo Dienstmann, Fernanda Christtanini Koyama
{"title":"Homologous recombination deficiency test validation in patients with high-grade advanced ovarian cancer.","authors":"Angelica Nogueira Rodrigues, Andreza Karine de Barros Almeida Souto, Diocésio Alves Pinto de Andrade, Larissa Müller Gomes, Sandra Satie Koide, Renata de Godoy E Silva, Bruno Batista de Souza, Juliana Doblas Massaro, Andréia Cristina de Melo, Andrea Morais Borges, Camila Giro, Carlos Augusto Vasconcelos de Andrade, Cesar Martins da Costa, Daniel Luiz Gimenes, Eduardo Caminha Bandeira de Mello, Fernanda Cesar de Oliveira, Frederico Müller de Toledo Lima, Gabriel Lima Lopes, Gustavo de Oliveira Bretas, Gustavo Guerra Jacob, Herika Lucia da Costa Silva, Juliana Ferrari Notaro, Lara Ladislau Alves, Marcos Veloso Moitinho, Mirian Cristina da Silva, Roberto Abramoff, Thais Amaral da Cunha Rauber, Rodrigo Dienstmann, Fernanda Christtanini Koyama","doi":"10.3389/fmolb.2025.1524594","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Along with <i>BRCA</i> 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 <i>BRCA</i>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.</p><p><strong>Objective: </strong>To technically validate an <i>in-house</i> next-generation sequencing (NGS)-based HRD test, QIAseq Custom Panel (QIAGEN), by comparing it with the reference assay, MyChoice CDx® Plus HRD (Myriad Genetics), which is used in routine care.</p><p><strong>Methods: </strong>This is a prospective cohort study conducted at the Oncoclínicas 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 Oncoclínicas and Co. We assessed the performance of the in-house test (GS Focus HRD) using Cohen's kappa statistic to measure agreement with the gold standard assay (MyChoice® HRD Plus CDx) in HRD status classification, along with other accuracy metrics.</p><p><strong>Results: </strong>In total, 41 samples were analyzed (20 HRD-positive, 19 HRD-negative, and 2 inconclusive results with the MyChoice® 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: 0.60-0.98). Overall accuracy, sensitivity, and specificity were 90%. Six samples had <i>BRCA1</i>/<i>2</i> mutations identified by the MyChoice® HRD Plus CDx, all of which were detected by the GS Focus HRD test.</p><p><strong>Conclusion: </strong>In summary, the results demonstrate substantial agreement and high accuracy of the NGS-based GS Focus HRD test compared to MyChoice® HRD Plus CDx. Our in-house assay is eligible for diagnostic test approval and market access as per Brazilian regulations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1524594"},"PeriodicalIF":3.9000,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850238/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Biosciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fmolb.2025.1524594","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Along with BRCA 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 BRCA1/2 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.
Objective: To technically validate an in-house next-generation sequencing (NGS)-based HRD test, QIAseq Custom Panel (QIAGEN), by comparing it with the reference assay, MyChoice CDx® Plus HRD (Myriad Genetics), which is used in routine care.
Methods: This is a prospective cohort study conducted at the Oncoclínicas 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 Oncoclínicas and Co. We assessed the performance of the in-house test (GS Focus HRD) using Cohen's kappa statistic to measure agreement with the gold standard assay (MyChoice® HRD Plus CDx) in HRD status classification, along with other accuracy metrics.
Results: In total, 41 samples were analyzed (20 HRD-positive, 19 HRD-negative, and 2 inconclusive results with the MyChoice® 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: 0.60-0.98). Overall accuracy, sensitivity, and specificity were 90%. Six samples had BRCA1/2 mutations identified by the MyChoice® HRD Plus CDx, all of which were detected by the GS Focus HRD test.
Conclusion: In summary, the results demonstrate substantial agreement and high accuracy of the NGS-based GS Focus HRD test compared to MyChoice® HRD Plus CDx. Our in-house assay is eligible for diagnostic test approval and market access as per Brazilian regulations.
期刊介绍：
Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology.
Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life.
In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.
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