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作为一种工具,小鼠模型可用于理解 BRAF 驱动型甲状腺癌的进展。

Mouse Models as a Tool for Understanding Progression in Braf-Driven Thyroid Cancers.

机构信息

Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

Endocrinol Metab (Seoul). 2019 Mar;34(1):11-22. doi: 10.3803/EnM.2019.34.1.11. Epub 2019 Feb 15.

Abstract

The development of next generation sequencing (NGS) has led to marked advancement of our understanding of genetic events mediating the initiation and progression of thyroid cancers. The NGS studies have confirmed the previously reported high frequency of mutually-exclusive oncogenic alterations affecting and proto-oncogenes in all stages of thyroid cancer. Initially identified by traditional sequencing approaches, the NGS studies also confirmed the acquisition of alterations that inactivate tumor protein p53 () and activate phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha () in advanced thyroid cancers. Novel alterations, such as those in telomerase reverse transcriptase () promoter and mating-type switching/sucrose non-fermenting (SWI/SNF) complex, are also likely to promote progression of the -driven thyroid cancers. A number of genetically engineered mouse models (GEMM) of -driven thyroid cancer have been developed to investigate thyroid tumorigenesis mediated by oncogenic BRAF and to explore the role of genetic alterations identified in the genomic analyses of advanced thyroid cancer to promote tumor progression. This review will discuss the various GEMMs that have been developed to investigate oncogenic -driven thyroid cancers.

摘要

下一代测序(NGS)的发展极大地促进了我们对遗传事件的理解,这些事件介导了甲状腺癌的发生和进展。NGS 研究证实了先前报道的在所有甲状腺癌阶段中,影响 和 原癌基因的相互排斥的致癌改变的高频率。这些改变最初是通过传统测序方法确定的,NGS 研究还证实了在晚期甲状腺癌中获得了失活肿瘤蛋白 p53()和激活磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位α()的改变。新的改变,如端粒酶逆转录酶()启动子和交配型转换/蔗糖非发酵(SWI/SNF)复合物的改变,也可能促进 - 驱动的甲状腺癌的进展。已经开发了多种 - 驱动的甲状腺癌的基因工程小鼠模型(GEMM),以研究致癌 BRAF 介导的甲状腺肿瘤发生,并探索在晚期甲状腺癌的基因组分析中确定的遗传改变在促进肿瘤进展中的作用。这篇综述将讨论为研究致癌 - 驱动的甲状腺癌而开发的各种 GEMM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b138/6435851/4d0716c070d8/enm-34-11-g001.jpg

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