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

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, Kalyani Chadalavada, Gouri J. Nanjangud, Ian Ganly, Nadeem Riaz, Alan L. Ho, Cristina R. Antonescu, Ronald Ghossein, Göran Stenman, Timothy A. Chan () and Luc G. T. Morris ()
Additional contact information
Martin G. Dalin: Memorial Sloan Kettering Cancer Center
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
Alexis Desrichard: 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
Deepa Ramaswami: Memorial Sloan Kettering Cancer Center
Jonathan J. Havel: Memorial Sloan Kettering Cancer Center
Fengshen Kuo: 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
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
Luc G. T. Morris: Memorial Sloan Kettering Cancer Center

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01178-z

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