Shortcomings of current methods of prostate cancer detection draw attention to a need for improved biomarkers. The TMPRSS2:ERG gene fusion leads to the overexpression of ERG, an ETS family transcription factor, and is the most prevalent genetic lesion in prostate cancer, but its clinical utility remains to be defined. Two radical prostatectomy samples were analysed by next-generation whole transcriptome sequencing. The chosen samples differed in fusion gene status, as previously determined by RT-PCR. The involvement of novel and previously reported prostate cancer-related transcripts, Wnt signalling, p53 effector loss and several ETS-regulated pathways was identified in the prostate cancer cases examined. ERG was found to directly transactivate RhoGDIB, a gene associated with fusion-positive prostate cancer. Overexpression of RhoGDIB elicited spindle-shaped morphology, faster cell migration and increased cell proliferation, phenotypic changes suggestive of cancer progression. The present findings confirm the value of comprehensive sequencing for biomarker development and indicate avenues of future study.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33381 |
| Date | 21 November 2012 |
| Creators | Chow, Anthony |
| Contributors | Seth, Arun |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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