Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions. Academic Article uri icon

Overview

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.

publication date

  • October 30, 2017

Research

keywords

  • Genomics
  • Myoepithelioma
  • Oncogene Fusion
  • Oncogene Proteins, Fusion
  • Salivary Gland Neoplasms

Identity

PubMed Central ID

  • PMC5662567

Scopus Document Identifier

  • 85032588771

Digital Object Identifier (DOI)

  • 10.1093/bioinformatics/btv639

PubMed ID

  • 29084941

Additional Document Info

volume

  • 8

issue

  • 1