Genetic profile of insertion mutations in mouse leukemias and lymphomas

被引:47
作者
Hansen, GM [1 ]
Skapura, D [1 ]
Justice, MJ [1 ]
机构
[1] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
关键词
D O I
10.1101/gr.10.2.237
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Murine leukemia retroviruses (MuLVs) cause leukemia and lymphoma in susceptible strains of mice as a result of insertional mutation of cellular proto-oncogenes or tumor suppressor genes. Using a novel approach to amplify and sequence viral insertion sites, we have sequenced >200 viral insertion sites from which we identify >35 genes altered by viral insertion in four AKXD mouse strains. The class of genes most frequently altered are transcription factors, however, insertions are found near genes involved in signal transduction, cell cycle control, DNA repair, cell division, hematopoietic differentiation, and near many ESTs and novel loci. Many of these mutations identify genes that have not been implicated in cancer. By isolating nearly all the somatic viral insertion mutations contributing to disease in these strains we show that each AKXD strain displays a unique mutation profile, suggesting strain-specific susceptibility to mutations in particular genetic pathways.
引用
收藏
页码:237 / 243
页数:7
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