Abstract 797: Glioblastoma animal model using CRISPR-Cas9 technology

Abstract

Current in vivo model system poses limitation on fully recapitulating genomic characteristics of a tumor due to high complexity and poor understanding of the heterogeneous microenvironment conditions in cancer pathogenesis. In an effort to address such issues, strategic models are required. In present study, we propose that the most representative cancer models have consistent tumor microenvironments and genomic mutations. The Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system is a powerful genome editing tool for efficient and precise genome engineering. Here, we employed CRISPR-Cas9 system in vivo to generate Cre-dependent Cas9 knock-in mouse (B6;129-Gt(ROSA)26Sortm1(CAG-cas9*,-EGFP)Fezh/J, Jackson lab.). The Cre-dependent Cas9 mouse models harbor combinations of genomic alterations including well-established oncogenes such as EGFRviii, c-MET, PDGFRa, IDH1 R132H and KRAS, EGFR, ALK, BRAF in Brain and Lung cancer models, respectively. While, they also consist of tumor suppressor genes including PTEN, NF1, Ink4a/ARF, Rb, TP53 and TP53, PTEN, NKx-1, APC in both Brain and Lung models, respectively. Cre-dependent model allows us to study in-depth into the tumor initiation and progression, while able to follow up in the role of tumor microenvironment in cancer maintenance. A better understanding of cancer models for preclinical research including their uses, as well as their limitations, may aid future potential studies regarding the development and implementation of new immune targeted therapies and potential validation of novel therapeutic biomarkers. Citation Format: Da Eun Jeong, Kee Hang Lee, Sung Soo Kim, Yoon Kyung Bae, Hyun Nam, Ji Yoon Hwang, Hee Jang Pyeon, Hye Jin Song, Kyeung Min Joo. Glioblastoma animal model using CRISPR-Cas9 technology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 797. doi:10.1158/1538-7445.AM2017-797