癌症的小鼠模型：用于插入诱变筛选和反向遗传学研究的睡美人转座子。
Mouse models of cancer: Sleeping Beauty transposons for insertional mutagenesis screens and reverse genetic studies.
机构信息
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA; Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA; Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
出版信息
Semin Cell Dev Biol. 2014 Mar;27:86-95. doi: 10.1016/j.semcdb.2014.01.006. Epub 2014 Jan 24.
The genetic complexity and heterogeneity of cancer has posed a problem in designing rationally targeted therapies effective in a large proportion of human cancer. Genomic characterization of many cancer types has provided a staggering amount of data that needs to be interpreted to further our understanding of this disease. Forward genetic screening in mice using Sleeping Beauty (SB) based insertional mutagenesis is an effective method for candidate cancer gene discovery that can aid in distinguishing driver from passenger mutations in human cancer. This system has been adapted for unbiased screens to identify drivers of multiple cancer types. These screens have already identified hundreds of candidate cancer-promoting mutations. These can be used to develop new mouse models for further study, which may prove useful for therapeutic testing. SB technology may also hold the key for rapid generation of reverse genetic mouse models of cancer, and has already been used to model glioblastoma and liver cancer.
癌症的遗传复杂性和异质性给设计合理靶向治疗以有效治疗大部分人类癌症带来了问题。对许多癌症类型的基因组特征分析提供了大量需要解释的数据，以进一步加深我们对这种疾病的理解。使用基于 Sleeping Beauty（SB）的插入诱变的小鼠正向遗传筛选是一种用于发现候选癌症基因的有效方法，有助于区分人类癌症中的驱动突变和乘客突变。该系统已被改编用于进行无偏筛选，以鉴定多种癌症类型的驱动因素。这些筛选已经确定了数百个候选致癌突变。这些可以用于开发新的小鼠模型进行进一步研究，这对于治疗测试可能是有用的。SB 技术也可能是快速生成癌症反向遗传小鼠模型的关键，并且已经用于模拟神经胶质瘤和肝癌。
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