文章：

利用转座子发现癌症基因

Harnessing transposons for cancer gene discovery

原文发布日期：2010-09-16

DOI: 10.1038/nrc2916

类型: Review Article

开放获取: 否

要点：

1. Transposon-based insertional mutagenesis (TIM) can be used to model many types of cancer in mice and facilitates the rapid identification of genes that cause cancer.
2. Comparison of the genes mutated by TIM with the genes mutated in human cancer can help to discriminate between those that are driver and those that are passenger mutations in human cancer.
3. TIM can identify new human cancer genes that have so far been missed in human cancer genome sequencing studies, that are difficult to identify because they are epigenetically regulated and that are located in large amplified or deleted regions.
4. TIM induces tumours at all stages of tumour progression, sometimes in a single animal. By identifying the genes mutated by TIM at each stage of progression it might be possible to determine the order in which the mutations were acquired and whether they are involved in tumour initiation, progression and metastasis.
5. Mouse cancer models induced by TIM provide a plethora of new models for studying the biology of cancer and for testing new cancer therapeutics before they go into the clinic.

要点翻译：

1. 基于转座子的插入突变（TIM）可用于模拟小鼠多种癌症类型，并能促进快速鉴定引发癌症的基因。
2. 将TIM突变基因与人类癌症突变基因进行比较，有助于区分人类癌症中的驱动突变和乘客突变。
3. TIM能够识别新的人类癌症基因，这些基因迄今在人类癌症基因组测序研究中被遗漏，或因表观遗传调控而难以识别，并位于大片段扩增或缺失区域。
4. TIM可在肿瘤进展的所有阶段诱导肿瘤，有时甚至在单个动物体内发生。通过识别TIM在肿瘤进展每个阶段突变的基因，有可能确定突变获得的顺序，以及它们是否参与肿瘤的发生、进展和转移。
5. TIM诱导的小鼠癌症模型为研究癌症生物学及在进入临床前测试新型癌症疗法提供了大量新模型。

英文摘要：

Recently, it has become possible to mobilize the Tc1/mariner transposon, Sleeping Beauty (SB), in mouse somatic cells at frequencies high enough to induce cancer. Tumours result from SB insertional mutagenesis of cancer genes, thus facilitating the identification of the genes and signalling pathways that drive tumour formation. A conditional SB transposition system has also been developed that makes it possible to limit where SB mutagenesis occurs, providing a means to selectively model many types of human cancer. SB mutagenesis has already identified a large collection of known cancer genes in addition to a plethora of new candidate cancer genes and potential drug targets.

摘要翻译： 

最近，已能在小鼠体细胞中以足够高的频率激活Tc1/mariner转座子Sleeping Beauty（SB），从而诱发癌症。肿瘤由SB插入突变致癌基因所致，因此便于鉴定驱动肿瘤形成的基因及信号通路。人们还开发了条件性SB转座系统，可限制SB突变发生的部位，为选择性模拟多种人类癌症提供手段。除大量已知癌基因外，SB突变还已发现众多新的候选癌基因和潜在药物靶点。

原文链接：

Harnessing transposons for cancer gene discovery