Identification of potential human oncogenes by mapping the common viral integration sites in avian nephroblastoma

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 repe...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2006, Vol.66 (1), p.78-86
Main Authors: PAJER, Petr, PECENKA, Vladimir, KRALOVA, Jarmila, KARAFIAT, Vit, PRUKOVA, Dana, ZEMANOVA, Zdena, KODET, Roman, DVORAK, Michal
Format: Article
Language:English
Subjects:
Animals
Avian Myeloblastosis Virus - genetics
Avian Proteins - genetics
Biological and medical sciences
Chick Embryo
Chickens
Chromosome Mapping
DNA-Binding Proteins - genetics
Genes, ras - genetics
Genes, Tumor Suppressor
Humans
Kidney Neoplasms - genetics
Kidney Neoplasms - virology
Kidneys
Medical sciences
Myeloblastosis-associated virus
Nephrology. Urinary tract diseases
Oncogene Proteins - genetics
Oncogenes - genetics
Polymerase Chain Reaction
Poultry Diseases - genetics
Proviruses - genetics
Terminal Repeat Sequences
Tumors of the urinary system
Twist-Related Protein 1 - genetics
Virus Integration - genetics
Wilms Tumor - genetics
Wilms Tumor - virology
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-05-1728