Title Automated scoring to assess RAD51-mediated homologous recombination in ovarian patient-derived tumor organoids /
Authors Thorel, Lucie ; Elie, Nicolas ; Morice, Pierre-Marie ; Weiswald, Louis-Bastien ; Florent, Romane ; Perréard, Marion ; Giffard, Florence ; Ricou, Agathe ; Leman, Raphaël ; Babin, Guillaume ; Lebrun, Jean-François ; Martin, Sandrine ; Briand, Mélanie ; Lambert, Bernard ; Joly, Florence ; Blanc-Fournier, Cécile ; Vaur, Dominique ; Dolivet, Enora ; Plancoulaine, Benoit Marc Edouard ; Poulain, Laurent
DOI 10.1016/j.labinv.2025.104097
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Is Part of Laboratory investigation.. New York : Elsevier B.V.. 2025, vol. 105, iss. 4, art. no. 104097, p. [1-11].. ISSN 0023-6837. eISSN 1530-0307
Keywords [eng] functional assay ; homologous recombination ; ovarian cancer ; patient-derived tumor organoids
Abstract [eng] Poly(ADP-ribose) polymerase inhibitors (PARPi) have been shown to improve progression-free survival, particularly in homologous recombination-deficient ovarian cancers. Identifying patients eligible for PARPi is currently based on next-generation sequencing, but the persistence of genomic scars in tumors after restoration of homologous recombination (HR) or epigenetic changes can be a limitation. Functional assays could thus be used to improve this profiling and faithfully identify homologous recombination-deficient tumors. The repair capacity (RECAP) test assesses the formation of RAD51 foci in proliferating cells after irradiation and can be used on tumors as well as on patient-derived tumor organoids (PDTO). However, RAD51 foci scoring is often performed manually without standardization. The purpose of this translational study was to develop an automated tool for scoring RAD51-mediated HR based on whole slide imaging of ovarian PDTO. To that end, we quantified Cyclin A2 and RAD51 immunofluorescence on 9 PDTO models derived from 8 ovarian cancer patients, and next, we compared the RECAP test results to genome instability score and to the patient clinical response. We therefore developed a standardized and automatized quantitative histoimaging tool allowing a comparative RAD51 foci evaluation and thus to define the HR status in PDTO. Our RECAP-based classification was correlated to the genome instability score, offering a new opportunity for standardization of HR assessment in PDTO. This new automated tool to score HR status, which remains to be validated on a large cohort of patients, may thus be used as a complement to next-generation sequencing-based tests in order to improve the identification of the number of patients eligible for PARPi.
Published New York : Elsevier B.V
Type Journal article
Language English
Publication date 2025
CC license CC license description