AUTHOR=Nogueira Rodrigues Angelica , Souto Andreza Karine de Barros Almeida , de Andrade Diocésio Alves Pinto , Gomes Larissa Müller , Koide Sandra Satie , e Silva Renata de Godoy , de Souza Bruno Batista , Massaro Juliana Doblas , de Melo Andréia Cristina , Borges Andrea Morais , Giro Camila , de Andrade Carlos Augusto Vasconcelos , da Costa Cesar Martins , Gimenes Daniel Luiz , de Mello Eduardo Caminha Bandeira , de Oliveira Fernanda Cesar , Lima Frederico Müller de Toledo , Lopes Gabriel Lima , Bretas Gustavo de Oliveira , Jacob Gustavo Guerra , Silva Herika Lucia da Costa , Notaro Juliana Ferrari , Alves Lara Ladislau , Moitinho Marcos Veloso , da Silva Mirian Cristina , Abramoff Roberto , Rauber Thais Amaral da Cunha , Dienstmann Rodrigo , Koyama Fernanda Christtanini 

TITLE=Homologous recombination deficiency test validation in patients with high-grade advanced ovarian cancer

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1524594

DOI=10.3389/fmolb.2025.1524594

ISSN=2296-889X

ABSTRACT=BackgroundAlong 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.ObjectiveTo 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.MethodsThis 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.ResultsIn 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.ConclusionIn 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.