1. Integrated Prostate Cancer Oncogenome Dataset 218 tumors (181 primaries, 37 metastases) 13 prostate cancer cell lines and xenografts Data collection: arrayCGH mRNA transcriptome (exon array) microRNAtranscriptome exonresequencing/mutation detection (157 genes) linked to clinical outcome (5 year median follow-up) William Gerald

2. Copy Number Alterations in Prostate Cancer Genomes 8-21% of primaries NCOA2 MYC 8q n = 194 tumors Barry Taylor, Chris Sander

3. NCOA2 amplifies AR pathway output in prostate cancer LNCaP cells Human tumors Vivek Arora, Haley Hieronymus

4. Overview of AR pathway alterations (expression outliers) Niki Schultz, Chris Sander

6. ERG may cooperate with other common alterations to drive prostate oncogenesis

7. Can we identify genetic events that cooperate with TMPRSS2-ERG to promote prostate oncogenesis?

9. p53 loss: Chr17 deletion spanning TP53 (q= 6e-3)

10. Multigenic 3p14 deletion containing several genes of interest (p = 5e-5)Barry Taylor

11. Multigenic 3p14 deletion enriched in TMPRSS2-ERG positive prostate cancer

12. Correlation between copy number loss and expression decreases for ERG-associated genes

13. Sequencing revealed SHQ1 point mutation,in addition to copy number truncation

17. Copy Number Alteration at Diagnosis and Time to Biochemical Relapse Barry Taylor, Brett Carver

18. This finding raises the possibility of knowing who need aggressive therapy right away (surgery, radiation, etc) and who can be followed with active surveillance. Next steps evaluate the gene copy number hypothesis on 1000 tumors with 10 year follow-up miniaturize the gene copy number test to work on needle biopsies and on circulating tumor cells To determine whether CNAs predict disease-specific death in prostate cancer patients managed conservatively

19. Acknowledgements AnuGopolan Nicholas Mitsiades Victor Reuter James Eastham Howard Scher Peter Scardino Yonghong Xiao William Gerald Barry Taylor Niki Schultz PoorviKaushik Chris Sander John E. Major Manda Wilson Nicholas D. Socci Alex Lash Haley Hieronymus Brett Carver VivekArora Charles Sawyers Thomas Landers Igor Dolgalev Adriana Heguy