title: Rearrangement of the ETS genes ETV-1, ETV-4, ETV-5, and ELK-4 is a clonal event during prostate cancer progression.
abstract: 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.
authors.affiliation: Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Alder
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.forename: Pavel
authors.initials: P
authors.lastname: Nikolov
authors.forename: Diana
authors.initials: D
authors.lastname: Boehm
authors.forename: Veit
authors.initials: V
authors.lastname: Scheble
authors.forename: Roopika
authors.initials: R
authors.lastname: Menon
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary; D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D050808:ets-Domain Protein Elk-4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C079853:ETV4 protein, human; C086680:ETV5 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D050808:ets-Domain Protein Elk-4