Retroviral Insertion Mutagenesis in Mice as a Comparative Oncogenomics Tool to Identify Disease Genes in Human Leukemia

Abstract

Retroviral insertion mutagenesis has recently received much attention because of its adverse effects in the application of retroviral vector-based gene therapy, resulting in leukemia in certain patients. At the same time, retroviral mutagenesis in mice is being considered a powerful forward genetic strategy to identify disease genes involved in cancer. The publication of the mouse genome sequence and the development of high-throughput genomic approaches have given a further boost to this rapidly evolving field. The increasing numbers of new potential oncogenes identified in retroviral screens have given a valuable basis for a better understanding of cancer related pathways in mice. Important challenges that now lie ahead of us are (i) to determine the relevance and causal relationship of these genes with various types of human cancer (ii) to develop strategies to identify tumor suppressor genes on a large scale, (iii) to place the disease genes into regulatory networks to better understand their role in the complex pathogenesis of cancer, and (iv) to determine their value for diagnosis refinement and therapeutic target intervention in human disease. In this review, we will give a brief update of the current state-of-the-art and thoughts concerning these issues. We will specifically focus on the value of employing retroviral insertion mutagenesis in mice and gene expression profiling in man in the context of acute myeloid leukemia.