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

Oncogene volume 24, pages 3419–3426 (2005)Cite this article

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 (ZiN c 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.

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Author notes

  1. Andre M Oliveira: Supported by Mayo Clinic and Mayo Clinic Foundation.

Authors and Affiliations

  1. Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA

    Andre M Oliveira, Paola Dal Cin, Chang-Jie Chen & Jonathan A Fletcher

  2. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Andre M Oliveira

  3. Department of Pathology, Children's Hospital, Boston, MA, USA

    Antonio R Perez-Atayde

  4. Departments of Orthopedic Surgery, Beth Israel Deaconess Medical Center and Children's Hospital Medical Center, Boston, MA, USA

    Mark C Gebhardt

  5. Department of Orthopaedic Surgery, University of Nebraska Medical Center, Omaha, NE, USA

    James R Neff

  6. Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    George D Demetri

  7. Department of Pathology, Massachusetts General Hospital, Boston, MA, USA

    Andrew E Rosenberg

  8. Department of Pathology, University of Nebraska Medical Center, Omaha, NE, USA

    Julia A Bridge

  9. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Jonathan A Fletcher

Authors
  1. Andre M Oliveira
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Correspondence to Andre M Oliveira or Jonathan A Fletcher.

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Oliveira, A., Perez-Atayde, A., Dal Cin, P. et al. Aneurysmal bone cyst variant translocations upregulate USP6 transcription by promoter swapping with the ZNF9, COL1A1, TRAP150, and OMD genes. Oncogene 24, 3419–3426 (2005). https://doi.org/10.1038/sj.onc.1208506

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