Rearrangement of the ETS Genes ETV-1, ETV-4, ETV-5 and LK-1 Is a Clonal Event during Prostate Cancer Progression
Martin Braun, Zaki Shaikibrahim, Pavel Nikolov, Diana Boehm, Wenzel Vogel, Roopika Menon, Veit Scheble, Falko Fend, Glen Kristiansen, Nicolas Wernert, Sven Perner. University Hospital of Bonn, Bonn, Germany; University Hospital of Tuebingen, Tuebingen, Germany
Background: ETS gene rearrangements are frequently found in prostate cancer (PCa). Several studies have assessed the rearrangement status of the most commonly found ETS gene, ERG, and the less frequent genes, ETV-1, ETV-4, ETV-5 and ELK-4 in primary PCa. However, the frequency in metastatic disease is still not well investigated. Recently, we have assessed the ERG rearrangement status in both primary PCa and the corresponding lymph node metastases, and observed that ERG rearrangement in primary PCa transfers into lymph node metastases, suggesting it to be a clonal expansion event during PCa progression. As a continuation, we investigated in this study whether this observation is valid also for the less frequent ETS rearranged genes ETV-1, ETV-4, ETV-5 and ELK-4.
Design: Using dual color break-apart FISH assays, we evaluated the status of all the less frequent ETS gene rearrangements for the first time on tissue microarrays (TMAs) constructed from a large cohort comprised of primary PCa and the corresponding lymph node metastases. Additionally, we evaluated the rearrangement status of all these ETS genes in a second cohort comprised of distant metastases.
Results: ETV-1, ETV-4, ETV-5 and ELK-4 rearrangements were found in 8/81 (10%), 5/85 (6%), 1/85 (1%) and 2/86 (2%) of the primary PCa, respectively, and in 6/73 (8%), 5/85 (6%), 4/72 (6%), 1/75 (1%) of the corresponding lymph node metastases, respectively. Rearrangements of ETV-1 and ETV-5 were not found in any of the distant metastases cases, whereas ETV-4 and ELK-4 rearrangements were found in 1/25 (4%) and 1/24 (4%) of the distant metastases, respectively.
Conclusions: Our results suggest that rearrangement of the less frequent ETS genes is a clonal event during prostate cancer progression. Our findings provide insights into potential clonal expansion events during PCa progression and may have significant implications in understanding the molecular basis of the metastatic cascade of PCa.
Category: Genitourinary (including renal tumors)
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 111, Tuesday Afternoon