Dr. Colin Collins and Dr. Stanislav Volik
Prostate cancer (PCa) is diagnosed in ~ 300,000 North American men annually. Invariably fatal metastatic prostate cancer is the second leading cause of cancer related deaths in men (~30,000 per year). Moreover, the incidence of prostate cancer is expected to rise with gains in longevity. Paradoxically, although metastatic prostate cancer is invariably fatal, because of its protracted natural history, 30-50% of men diagnosed with PCa may be able to avoid therapy and live with their disease. This is important because surgery and/or radiation can be associated with significant morbidities that diminish quality of life. Thus, there is an urgent need to differentiate primary tumors poised to seed metastasis from those that men can safely live with. Further, new biologic-based therapies are needed to treat terminal metastatic PCa. We employed aCGH and evolutionary logic to identify metastatic genotypes in early-stage tumors. This work provides evidence that biomarkers of metastasis can be identified in primary tumors and perhaps guide treatment decisions. However, array CGH cannot detect genome rearrangements, mutations, or pierce the haze of heterogeneity, thus limiting its ability to identify biomarkers and therapeutic targets. To overcome these limitations we pioneered paired-end sequencing methods for identifying changes in tumor DNA structure and gene expression. The application of aCGH and next generation sequencing technologies to the analysis of prostate tumor genomes and transcriptomes for identification of biomarkers and therapeutic targets will be discussed. Special challenges associated with analyzing NGS and microarray data and their integration with diverse data sets will be discussed.