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

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

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-g...

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Main 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
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Molecular Biosciences
Subjects:
ovarian cancer
homologous recombination deficiency
BRCA1/2
validation
next-generation sequencing
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2025.1524594/full
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Summary: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.
ISSN:2296-889X

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