作者
Titia G Meijer, Nicole S Verkaik, Anieta M Sieuwerts, Job van Riet, Kishan AT Naipal, Carolien HM van Deurzen, Michael A den Bakker, Hein FBM Sleddens, Hendrikus-Jan Dubbink, T Dorine den Toom, Winand NM Dinjens, Esther Lips, Petra M Nederlof, Marcel Smid, Harmen JG van de Werken, Roland Kanaar, John WM Martens, Agnes Jager, Dik C van Gent
发表日期
2018/12/15
期刊
Clinical cancer research
卷号
24
期号
24
页码范围
6277-6287
出版商
American Association for Cancer Research
简介
Purpose
Tumors of germline BRCA1/2 mutated carriers show homologous recombination (HR) deficiency (HRD), resulting in impaired DNA double-strand break (DSB) repair and high sensitivity to PARP inhibitors. Although this therapy is expected to be effective beyond germline BRCA1/2 mutated carriers, a robust validated test to detect HRD tumors is lacking. In this study, we therefore evaluated a functional HR assay exploiting the formation of RAD51 foci in proliferating cells after ex vivo irradiation of fresh breast cancer tissue: the recombination REpair CAPacity (RECAP) test.
Experimental Design
Fresh samples of 170 primary breast cancer were analyzed using the RECAP test. The molecular explanation for the HRD phenotype was investigated by exploring BRCA deficiencies, mutational signatures, tumor-infiltrating lymphocytes (TIL), and microsatellite instability (MSI …
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TG Meijer, NS Verkaik, AM Sieuwerts, J van Riet… - Clinical cancer research, 2018