Integrative Genomic Profiling of Human Prostate Cancer

Abstract

SUMMARY Annotation 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 percent 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 is now made available as a public resource.

Putative Prostate Cancer Risk SNP in an Androgen Receptor‐Binding Site of the Melanophilin Gene Illustrates Enrichment of Risk SNPs in Androgen Receptor Target Sites

“…In 56% of primary tumors and in almost all tumor metastases, androgen receptor (AR) is overexpressed and deregulated (Taylor, et al, 2010). Therefore, AR signaling has been both a main target for therapy and a focus in research for understanding the molecular mechanisms of PCa development and progression.…”

Novel approaches for the molecular classification of prostate cancer

“…In other tumor types including lung cancer, breast cancer and glioblastoma, genomic alterations have been relatively easily identified. However, from this study by Taylor et al [1] it appears that point mutations (single changes in the DNA sequence) may occur only rarely in prostate cancers. In fact, as the authors themselves conclude in their paper, there are no single genes that are commonly mutated in prostate cancer.…”

“…These approaches have utilized the latest technologies and sequencing capabilities to accomplish this goal. Two recent studies by Taylor et al [1] and Yu et al [2] are good examples of these approaches. Understanding the significance of these studies and their potential applications to prostate cancer is critical to reaching a better definition of the disease which impacts so many men.…”

“…Taylor et al [1] examined global DNA copy numbers (i.e. the numbers of copies of each gene) along with expression profiles (mRNAs that are expressed) to examine 218 prostate cancer tumors, both from individuals with localized disease as well as those with metastases.…”

“…Overall, the strengths of the study by Taylor et al [1], include the comprehensive nature of the genomic analysis that is performed. This is supported by strong clinical data that provides meaning to the studies being performed.…”