title: The MET gene is a common integration target in avian leukosis virus subgroup J-induced chicken hemangiomas.
abstract: Avian leukosis virus subgroup J (ALV-J) is a simple retrovirus that can cause hemangiomas and myeloid tumors in chickens and is currently a major economic problem in Asia. Here we characterize ALV-J strain PDRC-59831, a newly studied U.S. isolate of ALV-J. Five-day-old chicken embryos were infected with this virus, and the chickens developed myeloid leukosis and hemangiomas within 2 months after hatching. To investigate the mechanism of pathogenesis, we employed high-throughput sequencing to analyze proviral integration sites in these tumors. We found expanded clones with integrations in the MET gene in two of the five hemangiomas studied. This integration locus was not seen in previous work characterizing ALV-J-induced myeloid leukosis. MET is a known proto-oncogene that acts through a diverse set of signaling pathways and is involved in many neoplasms. We show that tumors harboring MET integrations exhibit strong overexpression of MET mRNA.
  
  
  OBJECTIVE
  These data suggest that ALV-J induces oncogenesis by insertional mutagenesis, and integrations in the MET oncogene can drive the overexpression of MET and contribute to the development of hemangiomas.
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: James
authors: J
authors: Justice
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Sanandan
authors: S
authors: Malhotra
authors: Department of Animal and Food Sciences, University of Delaware, Newark, Delaware, USA.
authors: Miguel
authors: M
authors: Ruano
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Yingying
authors: Y
authors: Li
authors: Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors: Guillermo
authors: G
authors: Zavala
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA.
authors: Nathan
authors: N
authors: Lee
authors: Department of Biological Sciences, University of Delaware, Newark, Delaware, USA.
authors: Robin
authors: R
authors: Morgan
authors: Department of Biology, Johns Hopkins University, Baltimore, Maryland, USA KLB@jhu.edu.
authors: Karen
authors: K
authors: Beemon
mesh_terms: D000818:Animals; D001353:Avian Leukosis / Q000821:virology*; D001354:Avian Leukosis Virus / Q000302:isolation & purification / Q000502:physiology*; D002645:Chickens; D006391:Hemangioma / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D014481:United States; D016662:Virus Integration
chemical_list: D019859:Proto-Oncogene Proteins c-met