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Primary prostate cancer can be characterized by molecular heterogeneity. However, systematic reviews of primary PCa and matched metastases in individual patients are lacking. We obtained 12 radical prostatectomy specimens from men who later developed metastatic castration-resistant prostate cancer in this pilot study. We then compared molecular profiles of these primary PCa areas to those of matched metastatic samples using whole-exome sequencing and amplicon-based DNA and RNA sequencing. Seven RP samples had monoclonal and topographically chronic disease, albeit with some degree of intratumor heterogeneity; four specimens had true multifocal disease and discontinuous topography, with one showing monoclonal disease with discontinuous topography; four others had true multifocal disease with discontinuous topography. Activating AR alterations were observed in nine mCRPC patients, but not in matched primary PCs. Overall, our findings support pathologic and molecular heterogeneity in primary PCas, and they indicate that thorough IHC-based pathology study and genomic analysis are especially relevant in nominating the ‘index' primary PCa area.
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