Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/6507
Title
Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling
Author(s)
Oldrini, Barbara CNIO | Curiel Garcia, Alvaro CNIO | Almeida Marques, Carolina CNIO | Matia Garcia, Veronica CNIO | Uluçkan, Azge CNIO | Graña Castro, Osvaldo CNIO | Torres Ruiz, Raul CNIC | Rodriguez Perales, Sandra CNIO | Huse, Jason T | Squatrito, Massimo CNIO
Date issued
2018-04-13
Citation
Nat Commun. 2018; 9(1): 1466.
Language
Inglés
Abstract
To accurately recapitulate the heterogeneity of human diseases, animal models require to recreate multiple complex genetic alterations. Here, we combine the RCAS-TVA system with the CRISPR-Cas9 genome editing tools for precise modeling of human tumors. We show that somatic deletion in neural stem cells of a variety of known tumor suppressor genes (Trp53, Cdkn2a, and Pten) leads to high-grade glioma formation. Moreover, by simultaneous delivery of pairs of guide RNAs we generate different gene fusions with oncogenic potential, either by chromosomal deletion (Bcan-Ntrk1) or by chromosomal translocation (Myb-Qk). Lastly, using homology-directed-repair, we also produce tumors carrying the homologous mutation to human BRAF V600E, frequently identified in a variety of tumors, including different types of gliomas. In summary, we have developed an extremely versatile mouse model for in vivo somatic genome editing, that will elicit the generation of more accurate cancer models particularly appropriate for pre-clinical testing.
Subject
IN-VIVO | CHROMOSOMAL REARRANGEMENTS | ACQUIRED-RESISTANCE | COLORECTAL-CANCER | TARGETED THERAPY | NERVOUS-SYSTEM | GENE-TRANSFER | LUNG-CANCER | MOUSE-LIVER | GLIOBLASTOMA
Online version
DOI
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