Data from A Fluorescence <i>In situ</i> Hybridization Screen for E26 Transformation–Specific Aberrations: Identification of DDX5-ETV4 Fusion Protein in Prostate Cancer

Abstract

<div>Abstract<p>Recurrent gene fusions involving E26 transformation–specific (ETS) transcription factors <i>ERG, ETV1, ETV4</i>, or <i>ETV5</i> have been identified in 40% to 70% of prostate cancers. Here, we used a comprehensive fluorescence <i>in situ</i> hybridization (FISH) split probe strategy interrogating all 27 ETS family members and their five known 5′ fusion partners in a cohort of 110 clinically localized prostate cancer patients. Gene rearrangements were only identified in ETS genes that were previously implicated in prostate cancer gene fusions including <i>ERG, ETV1</i>, and <i>ETV4</i> (43%, 5%, and 5%, respectively), suggesting that a substantial fraction of prostate cancers (estimated at 30–60%) cannot be attributed to an ETS gene fusion. Among the known 5′ gene fusion partners, <i>TMPRSS2</i> was rearranged in 47% of cases followed by <i>SLC45A3, HNRPA2B1</i>, and <i>C15ORF21</i> in 2%, 1%, and 1% of cases, respectively. Based on this comprehensive FISH screen, we have made four noteworthy observations. First, by screening the entire ETS transcription factor family for rearrangements, we found that a large fraction of prostate cancers (44%) cannot be ascribed to an ETS gene fusion, an observation which will stimulate research into identifying recurrent non-ETS aberrations in prostate cancers. Second, we identified <i>SLC45A3</i> as a novel 5′ fusion partner of <i>ERG</i>; previously, <i>TMPRSS2</i> was the only described 5′ partner of <i>ERG</i>. Third, we identified two prostate-specific, androgen-induced genes, <i>FLJ35294</i> and <i>CANT1</i>, as 5′ partners to <i>ETV1</i> and <i>ETV4</i>. Fourth, we identified a ubiquitously expressed, androgen-insensitive gene, <i>DDX5</i>, fused in frame with <i>ETV4</i>, leading to the expression of a DDX5-ETV4 fusion protein. [Cancer Res 2008;68(18):7629–37]</p></div>