BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1.

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. Here, we provide evidence that Btg1 knock out accelerates the development of a lethal lymphoproliferative disease driven by Bcl2 overexpression. Furthermore, we show that the scaffolding protein BCAR1 is a BTG1 partner. Moreover, after BTG1 deletion or expression of BTG1 mutations observed in patients with DLBCL, 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. © 2023 by The American Society of Hematology.

Citation

Lorric Delage, Mireille Lambert, Émilie Bardel, Cindy Kundlacz, Dimitri Chartoire, Axel Conchon, Anne-Laure Peugnet, Lucas Gorka, Patrick Auberger, Arnaud Jacquel, Carole Soussain, Olivier Destaing, Henri-Jacques Delecluse, Susanne Delecluse, Samir Merabet, Alexandra Traverse-Glehen, Gilles Salles, Emmanuel Bachy, Marc Billaud, Hervé Ghesquières, Laurent Genestier, Jean-Pierre Rouault, Pierre Sujobert. BTG1 inactivation drives lymphomagenesis and promotes lymphoma dissemination through activation of BCAR1. Blood. 2023 Mar 09;141(10):1209-1220

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PMID: 36375119

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