TY - JOUR T1 - Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions JF - bioRxiv DO - 10.1101/148072 SP - 148072 AU - Martin G. Dalin AU - Nora Katabi AU - Marta Persson AU - Ken-Wing Lee AU - Vladimir Makarov AU - Alexis Desrichard AU - Logan A. Walsh AU - Lyndsay West AU - Zaineb Nadeem AU - Deepa Ramaswami AU - Jonathan J. Havel AU - Fengshen Kuo AU - Kalyani Chadalavada AU - Gouri J. Nanjangud AU - Nadeem Riaz AU - Alan L Ho AU - Cristina R. Antonescu AU - Ronald Ghossein AU - Göran Stenman AU - Timothy A. Chan AU - Luc G.T. Morris Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/09/148072.abstract N2 - Myoepithelial carcinoma (MECA) is an aggressive type of salivary gland cancer with largely unknown molecular features. MECA may arise de novo or result from oncogenic transformation of a pre-existing pleomorphic adenoma (MECA ex-PA). We comprehensively analyzed the molecular alterations in MECA with integrated genomic analyses. We identified a low mutational load (0.5/MB), but a high prevalence of fusion oncogenes (28/40 tumors; 70%). We found FGFR1-PLAG1 in 7 (18%) cases, and the novel TGFBR3-PLAG1 fusion in 6 (15%) cases. TGFBR3-PLAG1 was specific for MECA de novo tumors or the malignant component of MECA ex-PA, was absent in 723 other salivary gland tumors, and promoted a tumorigenic phenotype in vitro. We discovered other novel PLAG1 fusions, including ND4-PLAG1, which is an oncogenic fusion between mitochondrial and nuclear DNA. One tumor harbored an MSN-ALK fusion, which was tumorigenic in vitro, and targetable with ALK inhibitors. Certain gene fusions were predicted to result in neoantigens with high MHC binding affinity. A high number of copy number alterations was associated with poorer prognosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future steps of diagnostic and therapeutic research in this lethal cancer. ER -