Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes

Andre M. Oliveira, Antonio R. Perez-Atayde, Paola Dal Cin, Mark C. Gebhardt, Chang Jie Chen, James R. Neff, George D. Demetri, Andrew E. Rosenberg, Julia A. Bridge, Jonathan A. Fletcher

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132 Scopus citations

Abstract

Aneurysmal bone cysts (ABC) are locally aggressive bone tumors that often feature chromosome 17p13 rearrangements. One of the ABC 17p13 rearrangements - t(16;17)(q22;p13) - was recently shown to create a CDH11-USP6 fusion in which the USP6/TRE17 oncogene is overexpressed through juxtaposition with the CDH11 promoter. Herein, we characterize four different ABC translocations involving 17p13, and we show that each is associated with a novel USP6 fusion oncogene. Specifically, we demonstrate that t(1;17), t(3;17), t(9;17), and t(17;17) result in USP6 fusions with TRAP150 (thyroid receptor-associated protein 150), ZNF9 (ZiNc Finger 9), Osteomodulin, and COL1A1 (Collagen 1A1), respectively. The oncogenic mechanism in these fusion genes is akin to CDH11-USP6, with the USP6 coding sequences juxtaposed to the promoter regions in each of the four novel translocation partners. The novel fusion partners appear well suited to drive USP6 transcription in the bone/mesenchymal context: osteomodulin is expressed strongly in osteoblastic lineages, and the COL1A1 promoter has an oncogenic role in the mesenchymal cancer dermatofibrosarcoma protuberans. In summary, these studies show that USP6 oncogenic activation results from heterogeneous genomic mechanisms involving USP6 transcriptional upregulation by juxtaposition with ectopic promoters.

Original languageEnglish (US)
Pages (from-to)3419-3426
Number of pages8
JournalOncogene
Volume24
Issue number21
DOIs
StatePublished - May 12 2005

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Keywords

  • Aneurysmal bone cyst
  • Translocation
  • USP6

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Oliveira, A. M., Perez-Atayde, A. R., Dal Cin, P., Gebhardt, M. C., Chen, C. J., Neff, J. R., Demetri, G. D., Rosenberg, A. E., Bridge, J. A., & Fletcher, J. A. (2005). Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene, 24(21), 3419-3426. https://doi.org/10.1038/sj.onc.1208506