PMC

Structure of ERG and TMPRSS2:ERG transcripts. Sequences derived from TMPRSS2 are shown in blue; sequences derived from ERG are shown in red. Light color, untranslated regions; heavy color, open reading frames predicted by tools available at http://www.dnalc.org/bioinformatics/dnalc_nucleotide_analyzer.htm#translator. The figure shows alternatively spliced variants of the normal ERG transcripts [ERG and ERG (−7)] and of the TMPRSS2:ERG hybrid transcripts [T1-E4 and T1-E4(−8)]. The spicing out of the 81-bp exon 7 (−7) in normal ERG transcripts and of the 72-bp exon 8 (−8) in TMPRSS2:ERG hybrid transcripts is predicted to occur in some prostate cancers based on the results of exon expression profiling (). The figure also shows the predicted structure of the T1-E2 TMPRSS2:ERG hybrid transcript. Expression data were only available for ERG exons 2 to 11; exon 1 was assumed to be present in the normal ERG transcripts.

Expression levels of the ERG gene. Right: Institute of Cancer Research: expression data from exons 4 to 11 of the ERG gene from 27 cancers determined in the current study using GeneChip Human Exon 1.0 ST arrays. Samples were designated as ERG rearrangement-positive (red dots) or ERG rearrangement-negative (blue dots) based on the presence of an altered ERG expression profile (see ). Cancer PRC25, which had a statistically significant elevated expression of exons 2 to 11, is marked. Left: Stephenson et al: expression data for the ERG gene determined using Affymetrix U133A human gene array as described previously. Data from each separate cancer sample is presented a black dot. The Stephenson dataset was normalized to our data by altering the complete expression distribution (including all genes and samples) such that the mean and variance were the same as those of the Institute of Cancer Research dataset.

Expression data for ERG exons 2 to 11 in prostate cancers determined using GeneChip Human Exon 1.0 ST arrays. Cancers scored as having altered ERG expression profiles based on the statistical analyses presented in are marked with an asterisk. In cancers designated as having altered ERG expression profiles, exon 8 of ERG was always expressed at lower levels than exons 4 to 7 and exons 9 to 11, indicating that this exon can be spliced out in rearranged ERG transcripts. In many of the cancers without altered ERG expression profiles, exon 7 was expressed at lower levels than exons 2 to 6 and exons 8 to 11, consistent with the presence of splice variants containing deletion of this 81-bp exon. The apparently depressed level of expression observed in some cancers (eg, PRC9) reflects the variation in observed level of ERG expression across the 27 cancers observed in this study, as illustrated in , and was not believed to reflect an abnormal ERG expression pattern. For each probe set within an exon, the log₂ ratio of the expression observed in the cancer to that observed in control non-neoplastic prostate epithelium was calculated. For each exon, the black dot represents the median of these values.