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Retroviruses and Insights into Cancer pp 285–305Cite as

Retroviruses as Tools to Identify Oncogenes and Tumor Suppressor Genes

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Abstract

The ability of retroviruses to disrupt host-gene expression is a significant factor in their oncogenic potential and this property has been harnessed in the use of retroviral insertional-mutagenesis (RIM) screens for the discovery of cancer genes. Targets for RIM include proto-oncogenes and tumor suppressors and, in some instances, microRNA (miRNA) loci. The mechanisms by which insertion can disrupt gene regulation are diverse, and the clustering of viral insertions at common insertion sites (CISs) can help to pinpoint regulatory elements in cellular gene loci. In the mouse, germline manipulation can be combined powerfully with RIM to identify collaborating and complementing gene sets and to favor the targeting of tumor-suppressor genes. The potential of RIM is far from exhausted, and the advent of improved methods for cloning insertion sites together with next generation sequencing technology promises to expand applications still further. With enlarged data sets, statistical analysis will become increasingly important to demonstrate significant clustering and avoid false discovery of CISs. While experimental systems are still largely confined to mouse models, the relevance of RIM to human leukaemia induced as a side effect of gene therapy trials is clear, highlighting the need for a better understanding of the risks presented by insertion elements, such as retroviral vectors.

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  1. Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow, Faculty of Veterinary Medicine, Glasgow, G61 1QH, UK

    James C. Neil

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  1. James C. Neil
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  2. Monica A. Stewart
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Correspondence to James C. Neil .

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  1. , Section of Molecular Genetics and Microb, University of Texas, Austin, One University Station, Austin, 78712-0162, Texas, USA

    Jaquelin Dudley

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Neil, J.C., Stewart, M.A. (2010). Retroviruses as Tools to Identify Oncogenes and Tumor Suppressor Genes. In: Dudley, J. (eds) Retroviruses and Insights into Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-09581-3_10

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