The RECAP Test Rapidly and Reliably Identifies Homologous Recombination-Deficient Ovarian Carcinomas

Recent studies have shown that the efficacy of PARP inhibitors in epithelial ovarian carcinoma (EOC) is related to tumor-specific defects in homologous recombination (HR) and extends beyond <i>BRCA1/2</i> deficient EOC. A robust method with which to identify HR-deficient (HRD) carcinomas...

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Bibliographic Details
Main Authors: Lise M. van Wijk, Sylvia Vermeulen, Matty Meijers, Manuela F. van Diest, Natalja T. ter Haar, Marthe M. de Jonge, Nienke Solleveld-Westerink, Tom van Wezel, Dik C. van Gent, Judith R. Kroep, Tjalling Bosse, Katja N. Gaarenstroom, Harry Vrieling, Maaike P. G. Vreeswijk
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/12/10/2805
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Summary:Recent studies have shown that the efficacy of PARP inhibitors in epithelial ovarian carcinoma (EOC) is related to tumor-specific defects in homologous recombination (HR) and extends beyond <i>BRCA1/2</i> deficient EOC. A robust method with which to identify HR-deficient (HRD) carcinomas is therefore of utmost clinical importance. In this study, we investigated the proficiency of a functional HR assay based on the detection of RAD51 foci, the REcombination CAPacity (RECAP) test, in identifying HRD tumors in a cohort of prospectively collected epithelial ovarian carcinomas (EOCs). Of the 39 high-grade serous ovarian carcinomas (HGSOC), the RECAP test detected 26% (10/39) to be HRD, whereas ovarian carcinomas of other histologic subtypes (<i>n</i> = 10) were all HR-proficient (HRP). Of the HRD tumors that could be sequenced, 8/9 showed pathogenic <i>BRCA1/2</i> variants or <i>BRCA1</i> promoter hypermethylation, indicating that the RECAP test reliably identifies HRD, including but not limited to tumors related to <i>BRCA1/2</i> deficiency. Furthermore, we found a trend towards better overall survival (OS) of HGSOC patients with RECAP-identified HRD tumors compared to patients with HRP tumors. This study shows that the RECAP test is an attractive alternative to DNA-based HRD tests, and further development of a clinical grade RECAP test is clearly warranted.
ISSN:2072-6694