Poster Presentation 28th Lorne Cancer Conference 2016

RNA-Seq of localized prostate cancer treated with “super castration” therapy (#177)

Natalie J Kurganovs 1 2 3 , Marek Cmero 4 5 , Nicholas Howard 1 , Pat Bugeja 1 2 , Michael Kerger 1 , David Clarke 2 , Phil Dundee 1 2 , Jeremy Grummet 6 7 , Justin Peters 2 4 , John Pederson 7 8 , Andrew Ryan 8 , Anthony Costello 1 2 4 , Paul Ruliancich 9 , Phillip Parante 7 9 , Christopher M Hovens 1 2 4 , Niall M Corcoran 1 2 4
  1. Australian Prostate Cancer Research Centre Epworth, Richmond, VIC, Australia
  2. Department of Surgery, Division of Urology, The Royal Melbourne Hospital, Parkville, VIC, Australia
  3. University of Melbourne, Parkville, VIC, Australia
  4. The University of Melbourne, Parkville, VIC, Australia
  5. Walter and Eliza Hall Institute , Parkville, Vic, Australia
  6. Alfred Hospital, Prahran, VIC, Australia
  7. Monash University, Clayton, VIC, Australia
  8. TissuPath Specialist Pathology Services, Mt Waverly, VIC, Australia
  9. Eastern Health and Epworth Eastern, Box Hill, VIC, Australia

The mainstay of treatment for prostate cancer is androgen deprivation therapy. Although this treatment initially aids survival by decreasing serum testosterone levels and reducing tumour burden, patients become castration resistant within 1-3 years. This is due to the maintenance of intraprostatic testosterone levels and the prevailing activity of the androgen receptor. Although cell lines and xenograft models allow the investigation of continued androgen receptor signaling after castration, they fail to represent the hormonal environment of prostate cancer patients. A neoadjuvant trial consisting of the "super-castration" treatment with bicalutamide, abiraterone and degarelix treatment for a period of 6 months prior to radical prostactomy was conducted. RNA and DNA has been extracted from 6 fresh frozen prostatectomy samples of the prostate following neoadjuvant treatment, and 7 hormone naïve prostate samples using Qiagen AllPrep DNA/RNA micro kit. RNA was used to construct a RNA-Seq library using NEBNext Ultra RNA Kit for Illumina and sequenced at a length of 150bp using paired end chemistry on an Illumina HiSeq. DeFuse and Jaffa were used to detect gene fusions, and edgeR was used to determine differential gene expression. Preliminary RNA-Seq data has shown a decrease in expression of androgen dependent genes, has detected both novel and already identified gene fusions, and identified activation of the calcium pathway and other key and novel pathways in the development of castration resistant prostate cancer.