Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

Abstract : The goal of this project is to develop biopsy based assays to assess the probability that patients with a negative biopsy or with a prostate cancer (CaP) Gleason score 6 (GS6) biopsy actually have significant CaP of Gleason score 7 or higher which was missed during the biopsy evaluations due to insufficient sampling. According to the DOD regulations, all research activities began after the approval of the research protocol by the HRPO at the end of March 2012. Since then, we have completed the transcriptomic profiling of the samples described in the original protocol. Furthermore, through additional funding and collaborations, we have significantly expanded the size and scope of the samples for genomic profiling. Transcriptomic profile (RNA-seq) of the expanded set of samples has been generated and mapped. We encountered some challenges in generating RRBS libraries from LCM samples which we overcame and we expect to have the RRBS data of the expanded set available shortly. Validation experiments were started by two new members of our team and are proceeding rapidly. Also, with the assistance of the biostatisticians in our group, case selection for all steps of the project is completed. Other research engagements funded separately, such as investigations of DNA-BPDE adducts and specific non-coding RNA in the benign tissues have promise in improving the accuracy of assays developed in this proposal. We are encouraged by our progress and are excited about the prospects of this research in improving the care of patients at risk of prostate cancer.