Characterization of the spectrum of trivalent VAV1-mutation-driven tumours using a gene-edited mouse model
[EN]Mutations in the VAV1 guanine nucleotide exchange factor 1 have been recently found in peripheral T cell lymphoma and nonsmall-cell lung cancer (NSCLC). To understand their pathogenic potential, we generated a gene-edited mouse model that expresses a VAV1 mutant protein that recapitulates the si...
| Autores: | , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/168603 |
| Acceso en línea: | http://hdl.handle.net/10366/168603 |
| Access Level: | acceso abierto |
| Palabra clave: | RAC1 TP53 Angioimmunoblastic T cell lymphoma Follicular helper T cells Nonsmall-cell lung cancer Peripheral T cell lymphoma Proto-Oncogene Proteins p21(ras) Mutant Proteins Mutation Animals Proto-Oncogene Proteins c-vav Neoplasms Mice 3207.13 Oncología neoplasias animales proteínas protooncogénicas c-vav ratones mutación proteínas mutantes proteínas protooncogénicas p21(ras) |
| Sumario: | [EN]Mutations in the VAV1 guanine nucleotide exchange factor 1 have been recently found in peripheral T cell lymphoma and nonsmall-cell lung cancer (NSCLC). To understand their pathogenic potential, we generated a gene-edited mouse model that expresses a VAV1 mutant protein that recapitulates the signalling alterations present in the VAV1 mutant subclass most frequently found in tumours. We could not detect any overt tumourigenic process in those mice. However, the concurrent elimination of the Trp53 tumour suppressor gene in them drives T cell lymphomagenesis. This process represents an exacerbation of the normal functions that wild-type VAV1 plays in follicular helper T cells. We also found that, in combination with the Kras oncogene, the VAV1 mutant version favours progression of NSCLC. These data indicate that VAV1 mutations play critical, although highly cell-type-specific, roles in tumourigenesis. They also indicate that such functions are contingent on the mutational landscape of the tumours involved. |
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