2026-06-14T03:31:39Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/65072025-05-13T11:16:08Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Oldrini, Barbara author Curiel Garcia, Alvaro author Almeida Marques, Carolina author Matia Garcia, Veronica author Uluçkan, Azge author Graña Castro, Osvaldo author Torres-Ruiz, Raul author Rodriguez Perales, Sandra author Huse, Jason T author Squatrito, Massimo author 2018-04-13 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. Nat Commun. 2018; 9(1): 1466. 10.1038/s41467-018-03731-w 2041-1723 2041-1723 Nature communications 29654229 http://hdl.handle.net/20.500.12105/6507 IN-VIVO CHROMOSOMAL REARRANGEMENTS ACQUIRED-RESISTANCE COLORECTAL-CANCER TARGETED THERAPY NERVOUS-SYSTEM GENE-TRANSFER LUNG-CANCER MOUSE-LIVER GLIOBLASTOMA Somatic genome editing with the RCAS-TVA-CRISPR-Cas9 system for precision tumor modeling