Identification of a novel recurrent EEF2 gene amplification in familial prostate tumours.

Recurrent tumour copy number variations (CNVs) in prostate cancer (PrCa) have predominantly been discovered in sporadic tumour cohorts. Here, we examined familial prostate tumours for novel CNVs as prior studies suggest these harbour distinct CNVs. Array comparative genomic hybridisation of twelve tumours from an Australian PrCa family, PcTas9, highlighted multiple recurrent CNVs, including amplification of EEF2 (19p13.3) in 100% of tumours. The EEF2 CNV was examined in a further 26 familial and seven sporadic tumours from the Australian cohort and in 494 tumours unselected for family history from The Cancer Genome Atlas (TCGA). EEF2 overexpression was observed in seven PcTas9 tumours, in addition to seven other predominantly familial tumours (n total =34%). EEF2 amplification was only observed in 1.4% of TCGA tumours, however 7.5% harboured an EEF2 deletion. Analysis of genes co-expressed with EEF2 revealed significant upregulation of two genes, ZNF74 and ADSL, and downregulation of PLSCR1 in both EEF2 amplified familial tumours and EEF2 deleted TCGA tumours. Furthermore, in TCGA tumours, EEF2 amplification and deletion were significantly associated with a higher Gleason score. In summary, we identified a novel PrCa CNV that was predominantly amplified in familial tumours and deleted in unselected tumours. Our results provide further evidence that familial tumours harbour distinct CNVs, potentially due to an inherited predisposition, but also suggest that regardless of how EEF2 is dysregulated, a similar set of genes involved in key cancer pathways are impacted. Given the current lack of gene-based biomarkers and clinical targets in PrCa, further investigation of EEF2 is warranted. This article is protected by copyright. All rights reserved.