利用 CRISPR/Cas9 在人细胞系模型中模拟人类癌症易感性综合征。
Modeling human cancer predisposition syndromes using CRISPR/Cas9 in human cell line models.
机构信息
Department of Pediatrics, University of Minnesota Twin Cities, Minneapolis, USA.
Comparative Molecular Biosciences PhD Program, University of Minnesota Twin Cities, Minneapolis, USA.
出版信息
Genes Chromosomes Cancer. 2023 Sep;62(9):493-500. doi: 10.1002/gcc.23140. Epub 2023 Apr 19.
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.
CRISPR 介导的基因工程的进步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。本综述重点介绍了使用 CRISPR/Cas9 基因组编辑工具来模拟各种人类癌症易感性综合征。我们研究了与神经纤维瘤病 1 型、Li-Fraumeni 综合征、Gorlin 综合征、BRCA 突变型乳腺癌和卵巢癌以及 APC 突变型癌症相关的遗传突变。此外，我们还讨论了使用下一代基于 CRISPR 的精确基因编辑工具将各种遗传损伤引入人类细胞系的可能性。目标是通过剖析这些突变对癌症发展的影响来提高这些癌症易感性综合征的临床前模型的质量，并为这些癌症易感性综合征的潜在机制提供新的见解。这些研究表明，CRISPR/Cas9 诱导的人类细胞系模型在研究癌症遗传基础方面具有持续的实用性和改进。
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