Integrative Genomic Profiling of Human Prostate Cancer

SummaryAnnotation of prostate cancer genomes provides a foundation for discoveries that can impact disease understanding and treatment. Concordant assessment of DNA copy number, mRNA expression, and focused exon resequencing in 218 prostate cancer tumors identified the nuclear receptor coactivator NCOA2 as an oncogene in ∼11% of tumors. Additionally, the androgen-driven TMPRSS2-ERG fusion was associated with a previously unrecognized, prostate-specific deletion at chromosome 3p14 that implicates FOXP1, RYBP, and SHQ1 as potential cooperative tumor suppressors. DNA copy-number data from primary tumors revealed that copy-number alterations robustly define clusters of low- and high-risk disease beyond that achieved by Gleason score. The genomic and clinical outcome data from these patients are now made available as a public resource.

► Integrated genomic profiling of 218 prostate tumors provides a unique public resource
► Androgen receptor coactivator NCOA2 is amplified in primary and metastatic disease
► TMPRSS2-ERG+ tumors associate with 3p14 loss and candidates FOXP1, RYBP, and SHQ1
► Degree and pattern of CNAs in primary tumors is associated with risk of relapse