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利用转座子进行癌症基因发现。

Harnessing transposons for cancer gene discovery.

机构信息

Genomics and Genetics Division, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, 61 Biopolis Drive, Proteos, Singapore 138673.

出版信息

Nat Rev Cancer. 2010 Oct;10(10):696-706. doi: 10.1038/nrc2916. Epub 2010 Sep 16.

DOI:10.1038/nrc2916
PMID:20844553
Abstract

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

最近,已经有可能在小鼠体细胞中以足够高的频率动员 Tc1/mariner 转座子、睡美人(SB),从而导致癌症。肿瘤是由 SB 插入突变致癌基因引起的,因此有助于鉴定驱动肿瘤形成的基因和信号通路。还开发了一种条件性 SB 转座系统,使得有可能限制 SB 突变发生的位置,从而提供了选择性模拟多种人类癌症的方法。SB 突变已经鉴定出大量已知的癌症基因,除了大量新的候选癌症基因和潜在的药物靶点。

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53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers.53BP1 缺失可挽救 BRCA1 缺陷,并与三阴性和 BRCA 突变型乳腺癌相关。
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Comparative analysis of transposable element vector systems in human cells.人类细胞中转座元件载体系统的比较分析。
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Tagged mutagenesis by efficient Minos-based germ line transposition.基于 Minos 的高效种系转座的标记诱变。
小鼠肠道类器官中的睡美人转座子诱变鉴定出参与肿瘤进展和转移的基因。
Cancer Gene Ther. 2024 Apr;31(4):527-536. doi: 10.1038/s41417-023-00723-x. Epub 2024 Jan 4.
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Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development.沉睡美人转座子突变导致的基因和通路参与炎症相关结肠肿瘤的发生。
Nat Commun. 2023 Oct 16;14(1):6514. doi: 10.1038/s41467-023-42228-z.
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Transposon Mutagenesis Reveals RBMS3 Silencing as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis.转座子诱变揭示 RBMS3 沉默促进 BRAFV600E 驱动的肺肿瘤发生的恶性进展。
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