2026-06-14T06:44:38Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/65072025-05-13T11:16:08Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Instituto de Salud Carlos III
funder
Fundación Seve Ballesteros
funder
Fundación BBVA
2018-10-24T09:01:08Z
2018-10-24T09:01:08Z
2018-04-13
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
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.
eng
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
journal article
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