Comment on “Insertional Mutagenesis”.
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In molecular biology, insertional mutagenesis is the creation of mutations of DNA by the addition of one or more base pairs. Such insertional mutations can occur naturally, mediated by viruses or transposons, or can be artificially created for research purposes in the lab.
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Recently, unusual forms of leukemias have developed as complications following retroviral transfer of potentially therapeutic genes into hematopoietic cells. A crucial component in the pathogenesis of these complications was the upregulation of a cellular proto-oncogene by random insertion of the retroviral gene transfer vector. These findings have great implications for the genetic manipulation of somatic stem cells in medicine. This review discusses the extent to which the random oncogene activation may have required disease-specific stimuli of the transgene and the hematopoietic milieu to become leukemogenic. Based on these considerations, we propose approaches to risk prediction and prevention.
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