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

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• PARP inhibitor efficacy in epithelial ovarian carcinoma (EOC) is linked to homologous recombination (HR) defects.
• HR deficiency (HRD) extends beyond BRCA1/2 mutations, necessitating reliable detection methods.
• Identifying HRD is crucial for guiding EOC treatment strategies.

Purpose of the Study:

• To evaluate the REcombination CAPacity (RECAP) test, a functional HR assay, for identifying HRD in prospectively collected EOCs.
• To assess the RECAP test's ability to detect HRD in high-grade serous ovarian carcinomas (HGSOC) and other subtypes.
• To compare RECAP test results with genetic sequencing and analyze overall survival (OS) trends.

Main Methods:

• Prospective collection of epithelial ovarian carcinoma (EOC) samples.
• Application of the REcombination CAPacity (RECAP) test, detecting RAD51 foci, to assess HR proficiency.
• Sequencing of HRD tumors to identify pathogenic variants or hypermethylation in BRCA1/2.
• Analysis of overall survival (OS) in relation to RECAP test results.

Main Results:

• The RECAP test identified 26% (10/39) of HGSOC as HRD.
• All other EOC histologic subtypes (n=10) were found to be HR-proficient (HRP).
• 8/9 sequenced HRD tumors showed BRCA1/2 variants or BRCA1 promoter hypermethylation, confirming RECAP test's accuracy.
• A trend towards better OS was observed in HGSOC patients with RECAP-identified HRD tumors compared to HRP tumors.

Conclusions:

• The RECAP test is a proficient functional assay for identifying HRD in EOC.
• The RECAP test reliably detects HRD, including cases not solely attributed to BRCA1/2 deficiency.
• The RECAP test presents a viable alternative to DNA-based HRD tests, warranting further clinical development.