Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions. Issue 1 (December 2017) - Dalin, Martin
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 thePLAG1 oncogene, which is associated withPLAG1 overexpression. We findFGFR1-PLAG1 in seven (18%) cases, and the novelTGFBR3-PLAG1 fusion in six (15%) cases.TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novelPLAG1 fusions includeND4-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, nominateTGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer. Myoepithelial carcinoma (MECA) is a rare aggressive salivary gland cancer. Here, the authors analyze the genomic landscape of MECA and identify a high prevalence of oncogenic gene fusions, primarily PLAG1 fusions, highlighting TGFBR3-PLAG1 as a potential hallmark of MECA.