Related Experiment Video

Updated: Sep 20, 2025

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
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Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

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Functional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based

Titia G Meijer1,2,3, Luan Nguyen4,5, Arne Van Hoeck4,5

  • 1Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. t.meijer@erasmusmc.nl.

Oncogene
|June 6, 2022
PubMed

Insights

The functional REpair CAPacity (RECAP) test identifies homologous recombination deficiency (HRD) tumors, including those not defined by DNA-based tests, suggesting broader utility for predicting Poly-[ADP-Ribose]-Polymerase inhibitor sensitivity in breast cancer patients.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Germline BRCA1/2 mutations predict Poly-[ADP-Ribose]-Polymerase (PARP) inhibitor response in breast cancer (BC).
  • Homologous recombination repair deficient (HRD) tumors, even without germline BRCA1/2 mutations, may also respond to PARP inhibitors.
  • Various HRD biomarkers are being investigated for clinical validity and utility.

Purpose of the Study:

  • To evaluate if the functional REpair CAPacity (RECAP) test identifies a similar group of HRD tumors as DNA-based HRD tests.
  • To assess the concordance between the RECAP test and established DNA-based HRD classifiers.

Main Methods:

  • An HRD-enriched cohort of 71 breast cancer patients was selected using the RECAP test.
  • Patients underwent DNA-based HRD testing, including the Classifier of HOmologous Recombination Deficiency (CHORD) and BRCA1/2-like classifier.
  • Whole genome sequencing (WGS) was performed on a subset of samples.

Main Results:

  • The RECAP test identified all 15 bi-allelic BRCA deficient samples in the cohort.
  • RECAP status showed partial correlation with DNA-based HRD tests, with 70% concordance for both RECAP-CHORD and RECAP-BRCA1/2-like classifiers.
  • The RECAP test identified additional HRD samples not detected by DNA-based tests, suggesting it captures deficiencies in other DNA repair genes.

Conclusions:

  • The functional RECAP test identifies a significant proportion of HRD tumors, including those missed by DNA-based assays.
  • RECAP may identify additional patients who could benefit from PARP inhibitor therapy.
  • Further clinical trials are needed to compare HRD tests for optimal predictive value in clinical decision-making.

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