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Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions

Author

Listed:
  • Martin G. Dalin

    (Memorial Sloan Kettering Cancer Center
    University of Gothenburg
    Sahlgrenska University Hospital)

  • Nora Katabi

    (Memorial Sloan Kettering Cancer Center)

  • Marta Persson

    (University of Gothenburg)

  • Ken-Wing Lee

    (Memorial Sloan Kettering Cancer Center)

  • Vladimir Makarov

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Alexis Desrichard

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Logan A. Walsh

    (Memorial Sloan Kettering Cancer Center)

  • Lyndsay West

    (Memorial Sloan Kettering Cancer Center)

  • Zaineb Nadeem

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Deepa Ramaswami

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Jonathan J. Havel

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Fengshen Kuo

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Kalyani Chadalavada

    (Memorial Sloan Kettering Cancer Center)

  • Gouri J. Nanjangud

    (Memorial Sloan Kettering Cancer Center)

  • Ian Ganly

    (Memorial Sloan Kettering Cancer Center)

  • Nadeem Riaz

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Alan L. Ho

    (Memorial Sloan Kettering Cancer Center)

  • Cristina R. Antonescu

    (Memorial Sloan Kettering Cancer Center)

  • Ronald Ghossein

    (Memorial Sloan Kettering Cancer Center)

  • Göran Stenman

    (University of Gothenburg)

  • Timothy A. Chan

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

  • Luc G. T. Morris

    (Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center
    Memorial Sloan Kettering Cancer Center)

Abstract

Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer.

Suggested Citation

  • Martin G. Dalin & Nora Katabi & Marta Persson & Ken-Wing Lee & Vladimir Makarov & Alexis Desrichard & Logan A. Walsh & Lyndsay West & Zaineb Nadeem & Deepa Ramaswami & Jonathan J. Havel & Fengshen Kuo, 2017. "Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01178-z
    DOI: 10.1038/s41467-017-01178-z
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