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

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

Authors:	Dalin, M. G.; Katabi, N.; Persson, M.; Lee, K. W.; Makarov, V.; Desrichard, A.; Walsh, L. A.; West, L.; Nadeem, Z.; Ramaswami, D.; Havel, J. J.; Kuo, F.; Chadalavada, K.; Nanjangud, G. J.; Ganly, I.; Riaz, N.; Ho, A. L.; Antonescu, C. R.; Ghossein, R.; Stenman, G.; Chan, T. A.; Morris, L. G. T.
Article Title:	Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions
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. © 2017 The Author(s).
Keywords:	clinical article; controlled study; human tissue; gene mutation; mutation; cancer recurrence; cancer staging; recurrence risk; phenotype; gene; gene overexpression; gene expression; cohort analysis; in vitro study; risk factor; risk assessment; carcinogenesis; genome analysis; oncogene; dna; gene fusion; fusion gene; genomics; salivary gland tumor; genetic risk; tumor; mitochondrial dna; copy number variation; myoepithelial carcinoma; research work; cell nucleus dna; disease incidence; cancer; human; male; female; article; mutational load; fgfr1 plag1 fusion gene; tgfbr3 plag1 fusion gene
Journal Title:	Nature Communications
Volume:	8
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2017-10-30
Start Page:	1197
Language:	English
DOI:	10.1038/s41467-017-01178-z
PROVIDER:	scopus
PMCID:	PMC5662567
PUBMED:	29084941
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032588771&doi=10.1038%2fs41467-017-01178-z&partnerID=40&md5=bb4c0aa0c836e87538ead686db3f645f
Notes:	Article -- Export Date: 4 December 2017 -- Source: Scopus