The MET Gene Is a Common Integration Target in Avian Leukosis Virus Subgroup J-Induced Chicken Hemangiomas

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 theMET 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 harboringMET integrations exhibit strong overexpression ofMET mRNA.IMPORTANCE These data suggest that ALV-J induces oncogenesis by insertional mutagenesis, and integrations in theMET oncogene can drive the overexpression ofMET and contribute to the development of hemangiomas.