Transcriptome Instability in Prostate Cancer

• Activity Number: 59
• Type: Topic Contributed
• Date/Time: Sunday, July 31, 2011 : 4:00 PM to 5:50 PM
• Sponsor: Section on Statistical Computing
• Author(s): Wei Li*+
• Companies: Baylor College of Medicine
• Keywords: cancer ; RNA-seq ; bioinformatics ; gene fusion ; instability

Abstract

We recently conducted an RNA-seq study in 20 primary PCa and 10 matched benign prostate tissues obtained from Baylor Prostate SPORE Tissue Core. We obtained in total 1.3 billion sequence reads, which lead to the identification of 46 highly-abundant gene fu-sion candidates, including TMPRSS2:ERG. Further experiments confirmed 27 novel gene fusions that were highly recurrent in PCa samples versus matched benign samples. Importantly, a subset of these fusions were present in PCa cell lines, but not in primary human prostate epithelial cells, implying their associations with cancer mechanisms. Their presence is also largely independent of expression of the parental genes, suggest-ing that other factors are involved in their production and regulation. One fusion gene, TMEM79-SMG5, is highly differentially expressed in PCa and therefore a potential biomarker. The prevalence of gene fusions may allow the limited number of human genes to encode substantially larger number of RNAs and proteins, forming an additional layer of cellular complexity. Together, our results suggest that gene fusions are widespread, and could have gr