title: The MYC, TERT, and ZIC1 genes are common targets of viral integration and transcriptional deregulation in avian leukosis virus subgroup J-induced myeloid leukosis.
abstract: The integration of retroviruses into the host genome following nonrandom genome-wide patterns may lead to the deregulation of gene expression and oncogene activation near the integration sites. Slow-transforming retroviruses have been widely used to perform genetic screens for the identification of genes involved in cancer. To investigate the involvement of avian leukosis virus subgroup J (ALV-J) integration in myeloid leukosis (ML) in chickens, we utilized an ALV-J insertional identification platform based on hybrid capture target enrichment and next-generation sequencing (NGS). Using high-definition mapping of the viral integration sites in the chicken genome, 241 unique insertion sites were obtained from six different ALV-J-induced ML samples. On the basis of previous statistical definitions, MYC, TERT, and ZIC1 genes were identified as common insertion sites (CIS) of provirus integration in tumor cells; these three genes have previously been shown to be involved in the malignant transformation of different human cell types. Compared to control samples, the expression levels of all three CIS genes were significantly upregulated in chicken ML samples. Furthermore, they were frequently, but not in all field ML cases, deregulated at the mRNA level as a result of ALV-J infection. Our findings contribute to the understanding of the relationship between multipathotypes associated with ALV-J infection and the molecular background of tumorigenesis.
  
  
  OBJECTIVE
  ALV-Js have been successfully eradicated from chicken breeding flocks in the poultry industries of developed countries, and the control and eradication of ALV-J in China are now progressing steadily. To further study the pathogenesis of ALV-J infections, it will be necessary to elucidate the in vivo viral integration and tumorigenesis mechanism. In this study, 241 unique insertion sites were obtained from six different ALV-J-induced ML samples. In addition, MYC, TERT, and ZIC1 genes were identified as the CIS of ALV-J in tumor cells, which might be a putative "driver" for the activation of the oncogene. In addition, the CIS genes showed deregulated expression compared to nontumor samples. These results have potentially important implications for the mechanism of viral carcinogenesis.
authors.affiliation: National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, South China Agricultural University, Guangzhou, People's Republic of China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
authors.forename: Xuemei
authors.initials: X
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yang
authors.forename: Chenggang
authors.initials: C
authors.lastname: Xu
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.forename: Jianru
authors.initials: J
authors.lastname: Qin
authors.forename: Manman
authors.initials: M
authors.lastname: Dai
authors.forename: Jianyong
authors.initials: J
authors.lastname: Hao
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Huang
authors.forename: Liqiang
authors.initials: L
authors.lastname: Tan
authors.forename: Weisheng
authors.initials: W
authors.lastname: Cao
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
mesh_terms: D000818:Animals; D001353:Avian Leukosis / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D001354:Avian Leukosis Virus / Q000235:genetics / Q000502:physiology*; D030161:Avian Proteins / Q000235:genetics / Q000378:metabolism; D002645:Chickens; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D011201:Poultry Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D016662:Virus Integration
chemical_list: D030161:Avian Proteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D019098:Telomerase