TY - JOUR
AU - Delage, Lorric
AU - Lambert, Mireille
AU - Bardel, Emilie
AU - Kundlacz, Cindy
AU - Chartoire, Dimitri
AU - Conchon, Axel
AU - Peugnet, Anne-Laure
AU - Gorka, Lucas
AU - Auberger, Patrick
AU - Jacquel, Arnaud
AU - Soussain, Carole
AU - Destaing, Olivier
AU - Delecluse, Henri-Jacques
AU - Delecluse, Susanne
AU - Merabet, Samir
AU - Traverse-Glehen, Alexandra
AU - Salles, Gilles A
AU - Bachy, Emmanuel
AU - Billaud, Marc
AU - Ghesquieres, Herve
AU - Genestier, Laurent
AU - Rouault, Jean Pierre
AU - Sujobert, Pierre
TI - BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1.
JO - Blood
VL - 141
IS - 10
SN - 0006-4971
CY - Washington, DC
PB - American Society of Hematology
M1 - DKFZ-2022-02815
SP - 1209-1220
PY - 2023
N1 - 2023 Mar 9;141(10):1209-1220
AB - Understanding the functional role of mutated genes in cancer is required to translate the findings of cancer genomics into therapeutic improvement. BTG1 is recurrently mutated in the MCD/C5 subtype of diffuse large B cell lymphoma (DLBCL), which is associated with extranodal dissemination. There, we provide evidence that Btg1 knock-out accelerates the development of a lethal lymphoproliferative disease driven by Bcl2 overexpression. We further show that the scaffolding protein BCAR1 is a BTG1 partner. Furthermore, following BTG1 deletion or expression of BTG1 mutations observed in DLBCL patients, the overactivation of the BCAR1-RAC1 pathway confers increased migration ability in vitro and in vivo. These modifications are targetable with the SRC inhibitor dasatinib, which opens novel therapeutic opportunities in BTG1 mutated DLBCL.
LB - PUB:(DE-HGF)16
C6 - pmid:36375119
DO - DOI:10.1182/blood.2022016943
UR - https://inrepo02.dkfz.de/record/182638
ER -