There are some shortcomings of using RNA transcripts as prostate cancer biomarkers, despite our ability to achieve very sensitive detection of TMPRSS2:ERG fusion variants. First, RNA is unstable and difficult to process in routine clinical assays. Second, commonly used drugs that inhibit androgen growth pathways, including GnRH agonists and testosterone antagonists, may diminish the production of the TMPRSS2:ERG mRNA fusion transcript, thereby producing false-negative results in patients on hormonal therapy with evolving androgenindependent tumors. Indeed, it has been reported that TMPRSS2:ERG mRNA fusion transcripts are not expressed in androgen-independent tumors in spite of the presence of interstitial deletions in between TMPRSS2 and ERG at chromosome 21q22 (10) . While FISH is useful for identifying genomic rearrangements, it has relatively lower resolution and is difficult to use in highly heterogeneous samples with small percentages of tumor cells. We have recently developed a technology, designated Primer Approximation Multiplex PCR (PAMP) for identifying breakpoints in genomic DNA without the need to purify cancer cells from normal tissues (26) . We are optimizing this assay for detecting the breakpoints between TMPRSS2 and ERG loci for primary prostate tumors to overcome any potential problems associated with RNA based biomarkers. In addition, the DNAbased assay will provide information about whether multiple fusion transcripts in a sample are derived from alternative splicing or tumor heterogeneity. The best approach may ultimately be to combine DNA and RNA based assays in a common format.