Abstract PO1-25-09: A new generation of breast cancer modeling has been achieved through somatic precision gene editing, offering high flexibility and efficiency

Abstract Breast cancer, along with many other cancers, is primarily caused by genetic mutations, typically involving the alteration of nucleotides (A, G, C, T) within genes (with a total of 12 possible mutations). Gene sequencing advancements have facilitated the identification of numerous gene mutations in tumor samples. However, comprehending the precise mechanisms through which these gene mutations contribute to tumor initiation, development, and their impact on tumor characteristics cannot be solely determined from these findings. Therefore, it is crucial to observe the influence of mutations on tumor initiation and development from the moment they occur. Since conducting such observations in human subjects is impractical, animal models with simulated gene mutations have become essential for studying tumor initiation and development. Mice, with a genome comprising approximately 2.7 billion nucleotides, are commonly used as animal models in cancer research due to their cost-effectiveness and high similarity to humans. About 90% of their genes share similar functions, particularly those associated with cancer development. However, achieving precise alterations to specific nucleotides among the 2.7 billion nucleotides within live mouse cells (with a total of 12 possible changes) has presented significant technical challenges. In this study, we present modifications to the CRISPR/Cas9 vector system, enabling homology-directed repair-mediated precise editing of any proto-oncogene in murine somatic mammary epithelial cells, thereby generating mammary tumor models with exceptional flexibility and efficiency. The resulting tumors exhibit significant advantages over traditional mouse models. This technological breakthrough bridges the gap between the potential of CRISPR technology and the accuracy of mouse models, facilitating the study of human tumor evolution and preclinical drug testing. Citation Format: Wen Bu, Yi li. A new generation of breast cancer modeling has been achieved through somatic precision gene editing, offering high flexibility and efficiency [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-25-09.