Rearrangement of the ETS genes ETV-1, ETV-4, ETV-5, and ELK-4 is a clonal event during prostate cancer progression

ETS gene rearrangements are frequently found in prostate cancer. Several studies have assessed the rearrangement status of the most commonly found ETS rearranged gene ERG, and the less frequent genes, ETV-1, ETV-4, ETV-5, and ELK-4 in primary prostate cancer. However, frequency in metastatic disease is not well investigated. Recently, we have assessed the ERG rearrangement status in both primary and corresponding lymph node metastases and observed that ERG rearrangement in primary prostate cancer transfers into lymph node metastases, suggesting it to be a clonal expansion event during prostate cancer progression. As a continuation, we investigated in this study whether this observation is valid for the less frequent ETS rearranged genes. Using dual-color break-apart fluorescent in situ hybridization assays, we evaluated the status of all less frequent ETS gene rearrangements for the first time on tissue microarrays constructed from a large cohort of 86 patients with prostate cancer and composed of primary and corresponding lymph node metastases, as well as in a second cohort composed of 43 distant metastases. ETV-1, ETV-4, ETV-5, and ELK-4 rearrangements were found in 8 (10%) of 81, 5 (6%) of 85, 1 (1%) of 85, and 2 (2%) of 86 of primary prostate cancer, respectively, and in 6 (8%) of 73, 4 (6%) of 72, 1 (1%) of 75, and 1 (1%) of 78 of corresponding lymph node metastases, respectively. ETV-1 and ETV-5 rearrangements were not found in the distant metastases cases, whereas ETV-4 and ELK-4 rearrangements were found in 1 (4%) of 25 and 1 (4%) of 24, respectively. Our findings suggest that rearrangement of the less frequent ETS genes is a clonal event during prostate cancer progression.