Poster Presentation 25th Lorne Cancer Conference 2013

L1 Retrotransposition and Somatic Genomic Instability in High-Grade Serous Ovarian Cancer   (#295)

Thu H M Nguyen 1 , Kyle Upton 1 , Geoff Faulkner 1
  1. Mater Medical Research Institute, South Brisbane , QLD, Australia

High-grade serous ovarian cancer accounts for over two thirds of all ovarian cancer cases, yet there are no screening tests or effective diagnostic tools currently available for early detection. Retrotransposons, present in all mammals, mobilise from one location of the genome to another via a copy-and-paste mechanism, and therefore can act as mutagens by directly disrupting exons or other regulatory regions, which could lead to genomic instability, and disregulation of normal cellular functions. Retrotransposition events have been implicated in more than 70 disease-causing mutations in humans. To investigate the role of LINE-1 retrotransposons in ovarian cancer, we will use both in-vitro and in-vivo analyses. Cell lines representative of the main classes of ovarian cancer have been transfected using a LINE-1 retrotransposition reporter assay to determine their potential to support retrotransposition. Results from this assay will be correlated with Western Blot analysis of ORF1p protein, as well as quantitative Real Time PCR analysis of LINE-1 expression. As cancer can have many causative elements, we will also conduct an in-depth genetic analysis using RNA-seq and SNP microarray analysis to determine the gene expression and single nucleotide polymorphism profiles as well as copy number variations of 20 human high-grade serous ovarian tumours against non-tumour or benign samples. To determine the contribution of LINE-1 retrotransposition, we will use Retrotransposon Capture Sequencing (RC-Seq) to map all germline retrotranposons, and identify novel retrotransposition events in these patients. Findings from this study will help elucidate the role of LINE-1 retrotransposons in ovarian cancer.