Dupuy Adam J, Jenkins Nancy A, Copeland Neal G
Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
Hum Mol Genet. 2006 Apr 15;15 Spec No 1:R75-9. doi: 10.1093/hmg/ddl061.
The National Cancer Institute and the National Human Genome Research Institute recently announced a 3-year 100-million-dollar pilot study to use large-scale resequencing of genes in human tumors to identify new cancer genes. The hope is that some of these genes can be used as drug targets for developing better therapeutics for treating cancer. Although this effort will identify new cancer genes, it could be made more efficient by preferentially resequencing genes identified as novel candidate cancer genes in animal models of cancer. Although retroviral insertional mutagenesis has proven to be an effective tool for identifying novel cancer genes in the mouse, these studies are limited by the fact that retroviral mutagenesis primarily induces hematopoietic and mammary cancer, but little else, while the majority of cancers affecting humans are solid tumors. Recently, two groups have shown that sleeping beauty (SB) transposon-based insertional mutagenesis can also identify novel candidate cancer genes in the mouse. Unlike retroviral infection, SB transposition can be controlled to mutagenize any target tissue and thus potentially induce many different kinds of cancer, including solid tumors. SB transposition in animal models of cancer could therefore greatly facilitate the identification of novel human cancer genes and the development of better cancer therapies.
美国国立癌症研究所和国家人类基因组研究所最近宣布了一项为期三年、耗资一亿美元的试点研究，旨在通过对人类肿瘤中的基因进行大规模重测序来识别新的癌症基因。人们希望其中一些基因能够用作药物靶点，以开发出更好的癌症治疗方法。尽管这项工作将识别出新的癌症基因，但通过优先对在癌症动物模型中被鉴定为新型候选癌症基因的基因进行重测序，可能会使其效率更高。虽然逆转录病毒插入诱变已被证明是在小鼠中识别新型癌症基因的有效工具，但这些研究存在局限性，即逆转录病毒诱变主要诱发造血系统和乳腺癌，其他类型的癌症很少诱发，而影响人类的大多数癌症是实体瘤。最近，两个研究小组表明，基于睡美人（SB）转座子的插入诱变也能够在小鼠中识别新型候选癌症基因。与逆转录病毒感染不同，SB转座可以被控制，从而诱变任何目标组织，进而有可能诱发许多不同类型的癌症，包括实体瘤。因此，在癌症动物模型中进行SB转座能够极大地促进新型人类癌症基因的识别以及更好的癌症治疗方法的开发。
