A gene expression profile of BRCAness that correlates with responsiveness to platinum and PARP inhibitors.

5004 Background: PARP inhibitors have been evaluated in patients with germline BRCA 1/2 mutations with impressive results. In addition to patients with germline BRCA 1/2 mutations, it has been suggested that PARP inhibition might also be a useful therapeutic strategy for the treatment of some patients with sporadic cancers. In order to better identify such patients, we defined a gene expression profile of “BRCAness” that correlates with responsiveness to platinum and PARP inhibitors. Methods: A publicly available microarray dataset including 61 patients with epithelial ovarian cancer with either sporadic disease or BRCA 1/2 mutations was used for development of the profile. Correlation with platinum responsiveness was assessed in platinum sensitive and resistant tumor biopsy specimens from 6 patients with BRCA germline mutations. Association with PARP inhibitor responsiveness and with radiation-induced RAD51 foci formation (a surrogate of homologous recombination) was assessed in Capan-1 cell line clones....