Oncology Abstracts

In a bid to discover genomic features associated with prostate cancer (PrCa) development and progression, copy number variations (CNVs) have been studied in tumour samples. Early comparative genomic hybridisation (CGH) studies led to the identification of many chromosomal regions of loss and gain, with a small number of these shown to be consistent across studies and, significantly, some suggested to be associated with PrCa progression. More recently a small number of studies have applied dense genome-wide SNP array platforms to fresh-frozen prostate tumours to identify recurrent CNVs, however these platforms are not suitable for the more widely available formalin-fixed, paraffin-embedded (FFPE) tumour samples. With the aim of replicating or identifying novel recurrent prostate tumour CNVs and elucidating the underlying genes involved, we applied the Agilent Oligonucleotide array-based CGH (aCGH), with both genome-wide and custom probes, to 12 FFPE prostate tumour DNA samples from a single Tasmanian family, PcTas9. Analysis of these data revealed as little as two to tens of CNVs present in each tumour, the majority of which were gains. In addition, several recurrent CNVs were identified, the most common of which was present on chromosome 19p13.3 and contained only two genes, including EEF2. EEF2 has recently been shown to be overexpressed in various cancer types, including breast and PrCa where it has been suggested to be associated with Gleason score. Currently, we are performing EEF2 gene and protein expression studies in tumour samples from PcTas9 and additional Tasmanian familial and sporadic PrCa cases, and will investigate whether these are associated with Gleason score. Our findings to date suggest that increased EEF2 protein levels observed in prior prostate tumour studies may be due to a copy number gain on 19p13.3.