2. Academic Validation
  3. Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions

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

  • Nat Commun. 2017 Oct 30;8(1):1197. doi: 10.1038/s41467-017-01178-z.
Martin G Dalin 1 2 3,  Nora Katabi 4,  Marta Persson 5,  Ken-Wing Lee 1,  Vladimir Makarov 1 6,  Alexis Desrichard 1 6,  Logan A Walsh 1,  Lyndsay West 7,  Zaineb Nadeem 1 7,  Deepa Ramaswami 1 7,  Jonathan J Havel 1 6,  Fengshen Kuo 1 6,  Kalyani Chadalavada 8,  Gouri J Nanjangud 8,  Ian Ganly 7,  Nadeem Riaz 6 9,  Alan L Ho 10,  Cristina R Antonescu 4,  Ronald Ghossein 4,  Göran Stenman 5,  Timothy A Chan 11 12 13,  Luc G T Morris 14 15 16
Affiliations

Affiliations

  • 1 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • 2 Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, 41685, Gothenburg, Sweden.
  • 3 Queen Silvia Children's Hospital, Sahlgrenska University Hospital, 41685, Gothenburg, Sweden.
  • 4 Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • 5 Sahlgrenska Cancer Center, Department of Pathology and Genetics, University of Gothenburg, 40530, Gothenburg, Sweden.
  • 6 Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • 7 Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • 8 Molecular Cytogenetics Core Facility, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • 9 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • 10 Head and Neck Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
  • 11 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. chant@mskcc.org.
  • 12 Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. chant@mskcc.org.
  • 13 Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. chant@mskcc.org.
  • 14 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. morrisl@mskcc.org.
  • 15 Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. morrisl@mskcc.org.
  • 16 Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. morrisl@mskcc.org.
PMID: 29084941 DOI: 10.1038/s41467-017-01178-z
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.

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