Chromosome rearrangement associated inactivation of tumour suppressor genes in prostate cancer

摘要: Prostate cancer, the most common male cancer in Western countries, is commonly detected with complex chromosomal rearrangements. Following discovery of recurrent TMPRSS2:ETS fusions prostate and EML4:ALK non-small-cell lung it now accepted that fusion genes not only are hallmark haematological malignancies sarcomas, but also play an important role epithelial cell carcinogenesis. However, previous studies aiming to identify were mainly focused on expression changes transcripts. To investigate recurrently affected by chromosome breakpoints we analysed Affymetrix array 6.0 500K SNP microarray data from 77 samples. While two frequently genomic were, as expected, ERG TMPRSS2, surprisingly more known tumour suppressor (TSGs) than oncogenes identified at breakpoints. Certain well-characterised TSGs, including p53, PTEN, BRCA1 BRCA2 truncated a result rearrangements cancer. Interestingly, many residing breakpoint sites have yet been implicated carcinogenesis such HOOK3, PPP2R2A TCBA1. We confirmed generally reduced selected clinical samples using quantitative RT-PCR analysis. Subsequently, further investigated associated t(4:6) translocation LNCaP cells reveal SNX9 putative TSG UNC5C, which led both genes. This study reveals another mechanism leads inactivation TSGs identification multiple inactivated will lead new direction research for molecular basis