Journal Article

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

Persson, Marta, Riaz, Nadeem, Chan, Timothy A., Ganly, Ian, Kuo, Fengshen, Katabi, Nora, Lee, Ken-Wing, Havel, Jonathan J., Desrichard, Alexis, Antonescu, Cristina R., Ramaswami, Deepa, Chadalavada, Kalyani, Stenman, Göran, Ho, Alan L., Nadeem, Zaineb, Dalin, Martin G., Makarov, Vladimir, Walsh, Logan A., Morris, Luc G. T., Nanjangud, Gouri J., Ghossein, Ronald, West, Lyndsay

2017

Overview

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. 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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/67/1536 / 631/67/1857 / 692/699/67/68 / adenoid cystic carcinoma / Cancer / Cancer and Oncology / Cancer och onkologi / Cell and Molecular Biology / Cell- och molekylärbiologi / Copy number / Deoxyribonucleic acid / Diagnostic systems / Dimensional analysis / DNA / family-members / Fibroblast growth factor receptor 1 / Genomic analysis / Humanities and Social Sciences / MecA protein / Mitochondrial DNA / multidisciplinary / mutations / Oral cancer / pleomorphic adenomas / prognostic-factors / Risk factors / Salivary gland / salivary-gland tumors / Science / Science & Technology - Other Topics / Science (multidisciplinary) / sequencing data / soft-tissue / somatic point / transgenic mice / Tumors / uterine leiomyomas