Abstract B04: RAD51 expression as a biomarker of homologous recombination deficiency in ovarian cancer

RAD51 is a critical component of the homologous recombination pathway, forming a nucleoprotein filament that enables strand exchange and templated error-free DNA repair. The tumor suppressors BRCA1 and BRCA2 interact with RAD51 to control its activity on DNA. Defects in homologous recombination in tumors are clinically relevant, with evidence of synthetic lethality of such cancers to poly ADP ribose polymerase (PARP) inhibitors.Mutations in RAD51 are uncommon in cancer, but aberrant over-expression of RAD51 has been reported as a mechanism to overcome a recombination defect in in-vitro models. However there are no large scale studies on RAD51 expression in clinically annotated data sets. Here we report a series of experiments to study RAD51 protein expression in ovarian cancer, a tumor type where recombination defects are prominent and being evaluated in several clinical trials of PARP inhibition. Analysis of DNA repair protein expression in formalin fixed clinical tissue is challenging, and our experiments highlight recent advances in quantitative microscopy that are generalizable to other clinical scenarios as well.We first evaluated several commercially available monoclonal antibodies to RAD51 using siRNA depleted cell blocks, to identify an appropriate reagent and staining conditions for formalin fixed paraffin embedded (FFPE) material. We then analyzed RAD51 expression in a collection of 600 ovarian cancer samples obtained through the British Columbia Cancer Agency (BCCA...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: New Technology and Bioinformatics: Poster Presentations - Proffered Abstracts Source Type: research