Abstract 334: Detection of BRCAness by a functional biomarker

Abstract

Homologous recombination (HR) is an error-free repair pathway to eliminate DNA double-strand breaks and cells with deficiency of HR repair are highly sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. Thus, targeting HR-defective cells becomes a new therapeutic approach for cancer patients. HR deficiency can be identified as BRCAness which may be due to mutations or epigenetic silencing in genes involved in HR, such as BRCA1 and BRCA2. Recent studies have developed several approaches to analyze HR status of cancer cells including RAD51 focus formation assay, large-scale mutational signatures analysis, and genome-wide transcriptome profiling. However, these assays provide an indirect estimation of HR status. We wish to directly measure HR rate in cancer cells. We have successfully developed two approaches, plasmid-based and virus-based functional assays, to directly quantify HR activity in cells and serve as a functional biomarker. Our results show that the signal of the functional biomarker specifically depends on the presence of the key enzyme, RAD51 recombinase, in HR. Finally, these functional assays can be utilized in different cancer cell types to determine the HR activity and can be a functional biomarker to evaluate the “BRCAness” status for the treatment of PARP inhibitors. Citation Format: Chih-Ying Lee, Min-Yu Ko, Kai-Hang Lei, Peter Chi. Detection of BRCAness by a functional biomarker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 334.