Identification of a novel recurrent EEF2 gene amplification in familial prostate tumors

Recurrent tumor copy number variations (CNVs) in prostate cancer (PrCa) have predominantly been discovered in sporadic tumor cohorts. Here, we examined familial prostate tumors for novel CNVs as prior studies suggest these harbor distinct CNVs. Array comparative genomic hybridization of 12 tumors from an Australian PrCa family, PcTas9, highlighted multiple recurrent CNVs, including amplification of <i>EEF2</i> (19p13.3) in 100% of tumors. The <i>EEF2</i> CNV was examined in a further 26 familial and seven sporadic tumors from the Australian cohort and in 494 tumors unselected for family history from The Cancer Genome Atlas (TCGA). <i>EEF2</i> overexpression was observed in seven PcTas9 tumors, in addition to seven other predominantly familial tumors (<i>n</i>_total = 34%). <i>EEF2</i> amplification was only observed in 1.4% of TCGA tumors, however 7.5% harbored an <i>EEF2</i> deletion. Analysis of genes co-expressed with <i>EEF2</i> revealed significant upregulation of two genes, ZNF74 and ADSL, and downregulation of PLSCR1 in both <i>EEF2</i> amplified familial tumors and <i>EEF2</i> deleted TCGA tumors. Furthermore, in TCGA tumors, <i>EEF2</i> 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 tumors and deleted in unselected tumors. Our results provide further evidence that familial tumors harbor distinct CNVs, potentially due to an inherited predisposition, but also suggest that regardless of how <i>EEF2</i> 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 <i>EEF2</i> is warranted.