LAUSR

more frequently in very-low-risk and low-risk prostate cancer tumours than in tumours in higher risk categories. Furthermore, fusions containing interstitial genes are less likely to be associated with biochemical recurrence. Identifying patients with fusion-positive cancer retaining interstitial genes could assist patient management, especially in terms of active surveillance. Investigators analysed TMPRSS2–ERG fusion in 133 prostate cancer samples that were stratified into four categories: very-low-risk, low-risk, intermediate-risk, and high-risk disease. Overall, TMPRSS2–ERG fusion was observed in 45% of the samples; specifically in 43%, 59%, 52%, and 24% of very-low-risk, low-risk, intermediate-risk, and high-risk cancers, respectively. Mate pair sequencing enabled genome-wide profiling of chromosomal rearrangements, revealing the predominance of fusions of TMPRSS2 exons 1 or 2 to ERG exons 3 or 4, meaning TMPRSS2 promoter function and ERG oncogenic functional domains were retained. Furthermore, copy number data obtained using mate pair sequencing showed that TMPRSS2– ERG fusion without interstitial deletion was significantly enriched in very-low-risk and low-risk tumours. Direct fusion was the most common mechanism of fusion (63% of ERG-positive samples). Complex rearrangement occurred in 37% of ERG-positive samples, which could be further divided into three classes. Complex events in the presence of standard direct fusion occurred in 19 samples, direct TMPRSS2–ERG fusion with independent nonrelated events affecting either TMPRSS2 or ERG occurred in three samples, and complex nondirect (5’)TMPRSS2–(3’)ERG fusion occurred in seven samples. The majority of complex fusion events occurred in very-low-risk cancers. Univariate analysis showed that ERG fusion without interstitial deletion was associated with significantly reduced incidence of biochemical recurrence compared with ERG-negative tumours and ERG-positive tumours with interstitial deletion. The risk profiles of tumours with ERG fusion and interstitial deletion were similar to the profiles of fusion-negative tumours. These data suggest that men whose prostate cancer contains TMPRSS2–ERG fusion that retains interstitial genes have better outcomes than those with fusion-negative cancer or fusion-positive cancer with interstitial region loss. This information could useful for stratifying and managing patients with newly diagnosed prostate cancer. Louise Stone P R O S TAT E C A N C E R