Role of BTG1 inactivation in lymphomagenesis and lymphoma dissemination

ABSTRACT: 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

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Laurent GENESTIER  

PROVIDER: MSV000089045 | MassIVE | Thu Mar 10 23:59:00 GMT 2022

REPOSITORIES: MassIVE