title: USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst.
abstract: Aneurysmal bone cyst (ABC) is a locally aggressive osseous lesion that typically occurs during the first two decades of life. ABC was regarded historically as a nonneoplastic process, but recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs. Herein we show that a recurring ABC chromosomal translocation t(16;17)(q22;p13) creates a fusion gene in which the osteoblast cadherin 11 gene (CDH11) promoter region on 16q22 is juxtaposed to the entire ubiquitin-specific protease USP6 (Tre2) coding sequence on 17p13. CDH11-USP6 fusion transcripts were demonstrated only in ABC with t(16;17) but other ABCs had CDH11 or USP6 rearrangements resulting from alternate cytogenetic mechanisms. CDH11 is expressed strongly in bone, and our findings implicate a novel oncogenic mechanism in which deregulated USP6 transcription results from juxtaposition to the highly active CDH11 promoter.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. amoliveira@parthers.org
authors.forename: Andre M
authors.initials: AM
authors.lastname: Oliveira
authors.forename: Bae-Li
authors.initials: BL
authors.lastname: Hsi
authors.forename: Stanislawa
authors.initials: S
authors.lastname: Weremowicz
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Rosenberg
authors.forename: Paola
authors.initials: P
authors.lastname: Dal Cin
authors.forename: Nora
authors.initials: N
authors.lastname: Joseph
authors.forename: Julia A
authors.initials: JA
authors.lastname: Bridge
authors.forename: Antonio R
authors.initials: AR
authors.lastname: Perez-Atayde
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
mesh_terms: D000293:Adolescent; D017824:Bone Cysts, Aneurysmal / Q000175:diagnosis / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002885:Chromosomes, Human, Pair 16; D002886:Chromosomes, Human, Pair 17; D010450:Endopeptidases / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D014178:Translocation, Genetic; D043222:Ubiquitin Thiolesterase
chemical_list: D015820:Cadherins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C086960:osteoblast cadherin; D010450:Endopeptidases; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase