Clinical features of the primary prostate tumor remain insufficient for clinicians to accurately define patients at highest risk of developing metastases. However, the primary tumor is the source of these metastases, and thus should contain information on its metastatic potential. We hypothesized that the combination of a primary tumors copy number alterations (CNAs) and genome-wide transcriptome information would give us more insight in the biology of metastases-prone localized disease. We designed a retrospective clinically matched cohort study of patients with high-risk localized prostate cancer who have been treated with radical prostatectomy. A cohort of patients who have developed metastases during long-term follow-up (M+ cohort) was matched with patients who did not develop clinical recurrence (M− cohort). Paraffin embedded tumor blocks were retrieved for tissue collection and used for DNA and RNA extraction. CNAs were analyzed using GISTIC and transcriptome analysis was performed using the Decipher GRID platform. Forty-four patients were withheld with both high quality CNA and gene expression data of which 19 are part of the M+ cohort and 25 of the M− cohort. GISTIC analysis showed distinct CNA profiles, with significantly more focal amplifications in the M+ cohort, whilst the M− cohort harbors a 6q15 deletion. Transcriptome-wide gene expression analysis allowed us to identify a selection of genes in the amplified or deleted regions that were up- or downregulated, respectively. Ongoing investigations are focused on identifying which of these genes are driving the primary tumors metastatic potential.
Funding: T Van den Broeck is holder of a doctoral fellowship of the Fund for Scientific Research Flanders (FWO). This work supported by research grants from the KU Leuven (GOA/15/017). Claessens F. is the principal investigator for all the grants previously mentioned.
Presenting author: Thomas Van den Broeck, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Email: firstname.lastname@example.org.