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Recurrent rearrangements of FOS and FOSB define osteoblastoma

Author

Listed:
  • Matthew W. Fittall

    (The Francis Crick Institute
    University College London Cancer Institute
    Wellcome Trust Sanger Institute)

  • William Mifsud

    (University College London Cancer Institute
    Wellcome Trust Sanger Institute
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Nischalan Pillay

    (University College London Cancer Institute
    Royal National Orthopaedic Hospital NHS Trust)

  • Hongtao Ye

    (Royal National Orthopaedic Hospital NHS Trust)

  • Anna-Christina Strobl

    (Royal National Orthopaedic Hospital NHS Trust)

  • Annelien Verfaillie

    (The Francis Crick Institute)

  • Jonas Demeulemeester

    (The Francis Crick Institute
    University of Leuven)

  • Lei Zhang

    (Memorial Sloan Kettering Cancer Center)

  • Fitim Berisha

    (Royal National Orthopaedic Hospital NHS Trust)

  • Maxime Tarabichi

    (The Francis Crick Institute
    Wellcome Trust Sanger Institute)

  • Matthew D. Young

    (Wellcome Trust Sanger Institute)

  • Elena Miranda

    (University College London Cancer Institute)

  • Patrick S. Tarpey

    (Wellcome Trust Sanger Institute)

  • Roberto Tirabosco

    (Royal National Orthopaedic Hospital NHS Trust)

  • Fernanda Amary

    (Royal National Orthopaedic Hospital NHS Trust)

  • Agamemnon E. Grigoriadis

    (Guy’s Hospital)

  • Michael R. Stratton

    (Wellcome Trust Sanger Institute)

  • Peter Loo

    (The Francis Crick Institute
    University of Leuven)

  • Cristina R. Antonescu

    (Memorial Sloan Kettering Cancer Center)

  • Peter J. Campbell

    (Wellcome Trust Sanger Institute)

  • Adrienne M. Flanagan

    (University College London Cancer Institute
    Royal National Orthopaedic Hospital NHS Trust)

  • Sam Behjati

    (Wellcome Trust Sanger Institute
    University of Cambridge)

Abstract

The transcription factor FOS has long been implicated in the pathogenesis of bone tumours, following the discovery that the viral homologue, v-fos, caused osteosarcoma in laboratory mice. However, mutations of FOS have not been found in human bone-forming tumours. Here, we report recurrent rearrangement of FOS and its paralogue, FOSB, in the most common benign tumours of bone, osteoblastoma and osteoid osteoma. Combining whole-genome DNA and RNA sequences, we find rearrangement of FOS in five tumours and of FOSB in one tumour. Extending our findings into a cohort of 55 cases, using FISH and immunohistochemistry, provide evidence of ubiquitous mutation of FOS or FOSB in osteoblastoma and osteoid osteoma. Overall, our findings reveal a human bone tumour defined by mutations of FOS and FOSB.

Suggested Citation

  • Matthew W. Fittall & William Mifsud & Nischalan Pillay & Hongtao Ye & Anna-Christina Strobl & Annelien Verfaillie & Jonas Demeulemeester & Lei Zhang & Fitim Berisha & Maxime Tarabichi & Matthew D. You, 2018. "Recurrent rearrangements of FOS and FOSB define osteoblastoma," Nature Communications, Nature, vol. 9(1), pages 1-6, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04530-z
    DOI: 10.1038/s41467-018-04530-z
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