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| Status |
Public on Oct 12, 2022 |
| Title |
Characterization of the spectrum of trivalent VAV1 mutation-driven tumors using a gene-edited mouse model |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
VAV1 mutations have been recently found in peripheral T cell lymphoma and non-small cell lung cancer. To understand their pathogenic potential, we generated a gene-edited mouse model that expresses a Vav1 mutant protein that recapitulates the signaling alterations present the VAV1 mutant subclass most frequently found in tumors. We could not detect any overt tumorigenic process in those mice. However, the concurrent elimination of the Trp53 tumor 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 an oncogenic Kras mutation, the Vav1 mutant version favors progression of non-small cell lung cancer. These data indicate that VAV1 mutations play critical, although highly cell typespecific roles in tumorigenesis. They also indicate that such functions are contingent on the mutational landscape of the tumors involved.
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| Overall design |
Splenocytes from control (Trp53KI/KI) and lymphoma-bearing animals (Trp53KI/KI;Vav1DC/DC)
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| Contributor(s) |
Robles-Valero J, Fernández-Nevado L, Cuadrado M, Lorenzo-Martín LF, Fernández-Pisonero I, Abad A, Redín E, Montuenga L, Martín-Zanca D, Bigas A, Mallo M, Dosil M, Bustelo XR |
| Citation(s) |
35895495 |
| Submission date |
Nov 19, 2021 |
| Last update date |
Oct 13, 2022 |
| Contact name |
L. Francisco Lorenzo-Martín |
| E-mail(s) |
luis.lorenzomartin@epfl.ch
|
| Organization name |
École Polytechnique Fédérale de Lausanne (EPFL)
|
| Lab |
Laboratory of Stem Cell Bioengineering
|
| Street address |
EPFL – SV – IBI – LSCB – Station 15
|
| City |
Lausanne |
| State/province |
Vaud |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
| |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (8)
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| GSM5696289 |
Splenic sample (control) rep4 |
| GSM5696290 |
Splenic sample from lymphoma-bearing animals rep1 |
| GSM5696291 |
Splenic sample from lymphoma-bearing animals rep2 |
| GSM5696292 |
Splenic sample from lymphoma-bearing animals rep3 |
| GSM5696293 |
Splenic sample from lymphoma-bearing animals rep4 |
|
| Relations |
| BioProject |
PRJNA781998 |
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