MassIVE MSV000089045

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Role of BTG1 inactivation in lymphomagenesis and lymphoma dissemination

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Description

BTG1 is recurrently mutated in the MCD/C5 subgroup of diffuse large B cell lymphoma (DLBCL), but the functions of this gene in lymphomagenesis have never been investigated so far. Here we provide evidence that Btg1 knock out accelerates the development of a lethal lymphoproliferative disease driven by Bcl2 overexpression. Exploring the clinical association between BTG1 mutation and extranodal dissemination, we discovered BCAR1 as a new BTG1 partner. Following BTG1 inactivation, overactivation of the BCAR1-RAC1 pathway induced major remodeling of the actin cytoskeleton and increased migration capacities of lymphoma cells in vitro and in vivo. These modifications were targetable with the SRC inhibitor dasatinib, which opens interesting clinical perspectives in BTG1 mutated DLBCL [doi:10.25345/C5736M52N] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: BTG1, Lymphoma, Dissemination, Migration

Contact

Principal Investigators:
(in alphabetical order) 		Laurent GENESTIER, Lymphoma Immuno Biology Team Centre international de Recherche en Infectiologie (CIRI) INSERM U1111 CNRS UMR5308 Universit e Claude Bernard Lyon I ENS de Lyon Hospices Civils de Lyon Facult e de M edecine Lyon Sud 165, Chemin du grand Revoyet BP 12 69921 OULLINS Cedex, FRANCE
Submitting User: Frederic

Publications

Delage L, Lambert M, Bardel É, Kundlacz C, Chartoire D, Conchon A, Peugnet AL, Gorka L, Auberger P, Jacquel A, Soussain C, Destaing O, Delecluse HJ, Delecluse S, Merabet S, Traverse-Glehen A, Salles G, Bachy E, Billaud M, Ghesquières H, Genestier L, Rouault JP, Sujobert P.
BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1.
Blood. 2023 Mar 9;141(10):1209-1220.

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