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睡美人诱变技术:利用正向遗传学筛选发现癌症基因。

Sleeping Beauty mutagenesis: exploiting forward genetic screens for cancer gene discovery.

作者信息

Mann Michael B, Jenkins Nancy A, Copeland Neal G, Mann Karen M

机构信息

Cancer Research Program, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, United States.

Cancer Research Program, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, United States.

出版信息

Curr Opin Genet Dev. 2014 Feb;24:16-22. doi: 10.1016/j.gde.2013.11.004. Epub 2013 Dec 20.

DOI:10.1016/j.gde.2013.11.004
PMID:24657532
Abstract

Sleeping Beauty (SB) is a powerful insertional mutagen used in somatic forward genetic screens to identify novel candidate cancer genes. In the past two years, SB has become widely adopted to model human pancreatic, hepatocellular, colorectal and neurological cancers to identify loci that participate in tumor initiation, progression and metastasis. Oncogenomic approaches have directly linked hundreds of genes identified by SB with human cancers, many with prognostic implications. These SB candidate cancer genes are aiding to prioritize punitive human cancer genes for follow-up studies and as possible biomarkers or therapeutic targets. This review highlights recent advances in SB cancer gene discovery, approaches to validate candidate cancer genes, and efforts to integrate SB data across all tumor types to prioritize drug development and tumor specificity.

摘要

“睡美人”(SB)是一种强大的插入诱变剂,用于体细胞正向遗传筛选以鉴定新型候选癌症基因。在过去两年中,SB已被广泛用于构建人类胰腺癌、肝细胞癌、结直肠癌和神经癌模型,以识别参与肿瘤起始、进展和转移的基因座。肿瘤基因组学方法已将数百个由SB鉴定出的基因与人类癌症直接联系起来,其中许多具有预后意义。这些SB候选癌症基因有助于确定需进一步研究的惩罚性人类癌症基因,并作为可能的生物标志物或治疗靶点。本综述重点介绍了SB癌症基因发现的最新进展、验证候选癌症基因的方法,以及整合所有肿瘤类型的SB数据以确定药物开发优先级和肿瘤特异性的努力。

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