A Gene Expression Profile of BRCAness that Predicts for Responsiveness to Platinum and PARP Inhibitors

Our results thus far support the hypothesis that the BRCAness profile is able to track diverse molecular mechanisms that cause defective homologous recombination HR and that it is associated with survival in patients with sporadic disease and clinical responsiveness to platinum. Specifically, application of the BRCAness profile in the TCGA EOC dataset can identify tumors that have defective HR due to overexpression of certain miRNAs, in the absence of known genetic and epigenetic abnormalities of the HR pathway. Furthermore, the HSP90 inhibitor 17-AAG enhances sensitivity of non-BRCA12 mutated ovarian cancer cells to DSB-inducing agents olaparib and carboplatin at very low, sublethal concentrations. Importantly, the mechanism for this synergistic effect seems to be increasing DNA damage via suppressing HR. Finally, high quality RNA from formalin fixed paraffin embedded ovarian cancer sections can be extracted and its detection and quantitation is highly concordant with that obtained from frozen tissue.