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dc.contributor.authorMeijer, Titia G
dc.contributor.authorNguyen, Luan
dc.contributor.authorVan Hoeck, Arne
dc.contributor.authorSieuwerts, Anieta M
dc.contributor.authorVerkaik, Nicole S
dc.contributor.authorLadan, Marjolijn M
dc.contributor.authorRuigrok-Ritstier, Kirsten
dc.contributor.authorvan Deurzen, Carolien HM
dc.contributor.authorvan de Werken, Harmen JG
dc.contributor.authorLips, Esther H
dc.contributor.authorLinn, Sabine C
dc.contributor.authorMemari, Yasin
dc.contributor.authorDavies, Helen
dc.contributor.authorNik-Zainal, Serena
dc.contributor.authorKanaar, Roland
dc.contributor.authorMartens, John WM
dc.contributor.authorCuppen, Edwin
dc.contributor.authorJager, Agnes
dc.contributor.authorvan Gent, Dik C
dc.date.accessioned2022-07-08T01:04:40Z
dc.date.available2022-07-08T01:04:40Z
dc.date.issued2022-06
dc.identifier.issn0950-9232
dc.identifier.otherPMC9232391
dc.identifier.other35662281
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338900
dc.description.abstractGermline BRCA1/2 mutation status is predictive for response to Poly-[ADP-Ribose]-Polymerase (PARP) inhibitors in breast cancer (BC) patients. However, non-germline BRCA1/2 mutated and homologous recombination repair deficient (HRD) tumors are likely also PARP-inhibitor sensitive. Clinical validity and utility of various HRD biomarkers are under investigation. The REpair CAPacity (RECAP) test is a functional method to select HRD tumors based on their inability to form RAD51 foci. We investigated whether this functional test defines a similar group of HRD tumors as DNA-based tests. An HRD enriched cohort (n = 71; 52 primary and 19 metastatic BCs) selected based on the RECAP test (26 RECAP-HRD; 37%), was subjected to DNA-based HRD tests (i.e., Classifier of HOmologous Recombination Deficiency (CHORD) and BRCA1/2-like classifier). Whole genome sequencing (WGS) was carried out for 38 primary and 19 metastatic BCs. The RECAP test identified all bi-allelic BRCA deficient samples (n = 15) in this cohort. RECAP status partially correlated with DNA-based HRD test outcomes (70% concordance for both RECAP-CHORD and RECAP-BRCA1/2-like classifier). RECAP selected additional samples unable to form RAD51 foci, suggesting that this functional assay identified deficiencies in other DNA repair genes, which could also result in PARP-inhibitor sensitivity. Direct comparison of these HRD tests in clinical trials will be required to evaluate the optimal predictive test for clinical decision making.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1476-5594
dc.sourcenlmid: 8711562
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectPoly(ADP-ribose) Polymerases
dc.subjectBRCA1 Protein
dc.subjectBRCA2 Protein
dc.subjectDNA
dc.subjectAntineoplastic Agents
dc.subjectFemale
dc.subjectHomologous Recombination
dc.subjectRecombinational DNA Repair
dc.subjectPoly(ADP-ribose) Polymerase Inhibitors
dc.titleFunctional RECAP (REpair CAPacity) assay identifies homologous recombination deficiency undetected by DNA-based BRCAness tests.
dc.typeArticle
dc.date.updated2022-07-08T01:04:39Z
prism.endingPage3506
prism.issueIdentifier26
prism.publicationNameOncogene
prism.startingPage3498
prism.volume41
dc.identifier.doi10.17863/CAM.86307
dcterms.dateAccepted2022-05-25
rioxxterms.versionofrecord10.1038/s41388-022-02363-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMeijer, Titia G [0000-0002-2235-6345]
dc.contributor.orcidvan de Werken, Harmen JG [0000-0002-9794-1477]
dc.contributor.orcidLips, Esther H [0000-0003-3488-4935]
dc.contributor.orcidDavies, Helen [0000-0001-6381-3664]
dc.contributor.orcidMartens, John WM [0000-0002-3428-3366]
dc.contributor.orcidvan Gent, Dik C [0000-0003-1473-8148]
dc.identifier.eissn1476-5594
pubs.funder-project-idKWF Kankerbestrijding (EMCR 2008-4045, EMCR 2014-7048)
pubs.funder-project-idKWF Kankerbestrijding (Dutch Cancer Society) (EMCR 2014-7048, EMCR 2008-4045)
cam.issuedOnline2022-06-03


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International