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Suzuki T, Shen H, Akagi K, Morse HC, Malley JD, Naiman DQ.. New genes involved in cancer identified by retroviral tagging. Nat Genet 32: 166-174

Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21702, USA.
Nature Genetics (Impact Factor: 29.65). 10/2002; 32(1):166-74. DOI: 10.1038/ng949
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ABSTRACT Retroviral insertional mutagenesis in BXH2 and AKXD mice induces a high incidence of myeloid leukemia and B- and T-cell lymphoma, respectively. The retroviral integration sites (RISs) in these tumors thus provide powerful genetic tags for the discovery of genes involved in cancer. Here we report the first large-scale use of retroviral tagging for cancer gene discovery in the post-genome era. Using high throughput inverse PCR, we cloned and analyzed the sequences of 884 RISs from a tumor panel composed primarily of B-cell lymphomas. We then compared these sequences, and another 415 RIS sequences previously cloned from BXH2 myeloid leukemias and from a few AKXD lymphomas, against the recently assembled mouse genome sequence. These studies identified 152 loci that are targets of retroviral integration in more than one tumor (common retroviral integration sites, CISs) and therefore likely to encode a cancer gene. Thirty-six CISs encode genes that are known or predicted to be genes involved in human cancer or their homologs, whereas others encode candidate genes that have not yet been examined for a role in human cancer. Our studies demonstrate the power of retroviral tagging for cancer gene discovery in the post-genome era and indicate a largely unrecognized complexity in mouse and presumably human cancer.

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    • "-myc, the EviN (N = 1, 2, 3,..) numbering system was applied by Copeland et al. to summarize the MLV integration site [Suzuki et al., 2002; Akagi et al, 2004] "
    Introduction to Sequence and Genome Analysis (BK025A), 01/2012; iConcept Press Ltd.
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    • " metastatic transforma tion ( Rhodes et al . , 2004 ) . High levels of Sox4 mRNA expression have been observed in a large number of human tumors including breast , lung , brain , prostate and ovarian cancer , and the Sox4 gene locus has been repeatedly found to be targeted by tumor - promoting retroviral integration in mice ( Lund et al . , 2002 ; Suzuki et al . , 2002 ; Shin et al . , 2004 ) . Together , these studies support the inclusion of Sox4 as one of the 64 genes that constitute a general cancer signature ( Rhodes et al . , 2004 ) . Sox4 may thus be considered as a master regulator of cell fate and differentiation in numerous cell types and appears to have a dominant role in the development of"
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    • "The non-random nature of viral integration and the potential for integration events to cause toxicity and cancer have long been realized [17] [18]. However, a formal VIS hot-spot definition was not described until the turn of the century when Suzuki et al. (2002) developed a definition for retroviral integration in cancer cells to discover potential cancer-related genes [19]. The authors referred to a hot-spot as a Common Insertion Site (CIS) and defined them as ≥4 integrations within a 100 kb region, 3 integrations within 50 kb or 2 within 30 kb. "
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