title: Identification of potential human oncogenes by mapping the common viral integration sites in avian nephroblastoma.
abstract: Gene deregulation is a frequent cause of malignant transformation. Alteration of the gene structure and/or expression leading to cellular transformation and tumor growth can be experimentally achieved by insertion of the retroviral genome into the host DNA. Retrovirus-containing host loci found repeatedly in clonal tumors are called common viral integration sites (cVIS). cVIS are located in genes or chromosomal regions whose alterations participate in cellular transformation. Here, we present the chicken model for the identification of oncogenes and tumor suppressor genes in solid tumors by mapping the cVIS. Using the combination of inverse PCR and long terminal repeat-rapid amplification of cDNA ends technique, we have analyzed 93 myeloblastosis-associated virus type 2-induced clonal nephroblastoma tumors in detail, and mapped >500 independent retroviral integration sites. Eighteen genomic loci were hit repeatedly and thus classified as cVIS, five of these genomic loci have previously been shown to be involved in malignant transformation of different human cell types. The expression levels of selected genes and their human orthologues have been assayed in chicken and selected human renal tumor samples, and their possible correlation with tumor development, has been suggested. We have found that genes associated with cVIS are frequently, but not in all cases, deregulated at the mRNA level as a result of proviral integration. Furthermore, the deregulation of their human orthologues has been observed in the samples of human pediatric renal tumors. Thus, the avian nephroblastoma is a valid source of cancer-associated genes. Moreover, the results bring deeper insight into the molecular background of tumorigenesis in distant species.
authors.affiliation: Institute of Molecular Genetics AS CR, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Pajer
authors.forename: Vladimír
authors.initials: V
authors.lastname: Pecenka
authors.forename: Jarmila
authors.initials: J
authors.lastname: Králová
authors.forename: Vít
authors.initials: V
authors.lastname: Karafiát
authors.forename: Dana
authors.initials: D
authors.lastname: Průková
authors.forename: Zdena
authors.initials: Z
authors.lastname: Zemanová
authors.forename: Roman
authors.initials: R
authors.lastname: Kodet
authors.forename: Michal
authors.initials: M
authors.lastname: Dvorák
mesh_terms: D000818:Animals; D009189:Avian Myeloblastosis Virus / Q000235:genetics; D030161:Avian Proteins / Q000235:genetics; D002642:Chick Embryo; D002645:Chickens; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000235:genetics; D016147:Genes, Tumor Suppressor; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000821:virology; D015513:Oncogene Proteins / Q000235:genetics; D009857:Oncogenes / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011201:Poultry Diseases / Q000235:genetics*; D011533:Proviruses / Q000235:genetics; D020079:Terminal Repeat Sequences; D051879:Twist-Related Protein 1 / Q000235:genetics; D016662:Virus Integration / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000821:virology
chemical_list: D030161:Avian Proteins; D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; C412362:Twist protein, Gallus gallus; D051879:Twist-Related Protein 1