Modeling human cancer predisposition syndromes using CRISPR/Cas9 in human cell line models.

Modeling human cancer predisposition syndromes using CRISPR/Cas9 in human cell line models.
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DOI:
10.1002/gcc.23140
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发表时间:
2023-09
影响因子:
3.7
通讯作者:
Largaespada, David A.
Largaespada, David A.
中科院分区:
医学2区
文献类型:
--
作者:
Draper, Garrett M.;Panken, Daniel J.;Largaespada, David A.
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CRISPR介导的基因工程的进展为改善癌症易感综合征的临床前人类细胞系模型提供了机会。这篇综述的重点是使用CRISPR/Cas9基因组编辑工具来模拟各种人类癌症易感综合征。我们研究了与1型神经纤维瘤病、Li-Fraumeni综合征、Gorlin综合征、BRCA突变型乳腺癌和卵巢癌以及APC突变型癌症相关的基因突变。此外,我们还讨论了使用下一代CRISPR衍生的精确基因编辑工具将各种遗传病变引入人类细胞系的可能性。我们的目标是通过剖析这些突变对癌症发展的影响,提高围绕这些癌症易感综合征的临床前模型的质量,并为这些癌症易感综合征的潜在机制提供新的见解。这些研究证明了CRISPR/Cas9诱导的人类细胞系模型在研究癌症遗传基础方面的持续效用和改进。
The advancement of CRISPR mediated gene engineering provides an opportunity to improve upon preclinical human cell line models of cancer predisposing syndromes. This review focuses on using CRISPR/Cas9 genome editing tools to model various human cancer predisposition syndromes. We examine the genetic mutations associated with neurofibromatosis type 1, Li-Fraumeni syndrome, Gorlin syndrome, BRCA mutant breast and ovarian cancers, and APC mutant cancers. Furthermore, we discuss the possibilities of using next-generation CRISPR-derived precision gene editing tools to introduce a variety of genetic lesions into human cell lines. The goal is to improve the quality of preclinical models surrounding these cancer predisposition syndromes through dissecting the effects of these mutations on the development of cancer and to provide new insights into the underlying mechanisms of these cancer predisposition syndromes. These studies demonstrate the continued utility and improvement of CRISPR/Cas9-induced human cell line models in studying the genetic basis of cancer.
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