REGULATION AND CLINICAL RELEVANCE OF RAD51 EXPRESSION IN CANCER

Abstract

RAD51 is a key recombination mediator that is overexpressed across various malignancies. The clinical relevance of RAD51 baseline expression in cancer is not clear, due to non-quantitative methods of measurement and heterogeneous cohorts in previous studies. Here, I optimize and quality control a multiplexed fluorescent immunohistochemistry protocol; an unique in-depth inquiry into quantitative in vivo data. I establish the RAD51 Vectra score, defined as baseline mean nuclear protein levels; epithelial ovarian cancers with higher score showed worse survival following carboplatin therapy. Next, I identify EZH2 as a novel regulator of baseline levels of RAD51, independent of cell cycle or the DNA damage response. Interestingly, EZH2 exerts its action on RAD51 expression through a methyltransferase-independent mechanism. In summary, high baseline RAD51 protein expression identifies a subgroup of epithelial ovarian cancers that may be suited to clinical trials of novel agents that do not rely on defective recombination.