TMPRSS2 fusions with oncogenic ETS factors in prostate cancer involve unbalanced genomic rearrangements and are associated with HDAC1 and epigenetic reprogramming.

摘要: Translocations fusing the strong androgen-responsive gene, TMPRSS2, with ERG or other oncogenic ETS factors may facilitate prostate cancer development. Here, we studied 18 advanced cancers for factor alterations, using reverse transcription-PCR and DNA RNA array technologies, identified putative downstream gene targets from microarray data of 410 samples. Out 27 factors, was most frequently overexpressed. Seven cases showed TMPRSS2:ERG fusions, whereas TMPRSS2:ETV4 fusion seen in one case. In five out six tumors high expression, array-CGH analysis revealed interstitial 2.8 Mb deletions between TMPRSS2 loci, smaller, unbalanced rearrangements. silico coexpression patterns an association expression histone deacetylase 1 low its target genes. Furthermore, observed increased WNT-associated pathways down-regulation tumor necrosis cell death pathways. summary, our indicate that translocation is common occurs by virtue genomic Activation lead to epigenetic reprogramming, WNT signaling, pathways, implicating several hallmarks potential therapeutic importance.