| Abstract: |
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 The American Society of Hematology |
| Keywords: |
controlled study; unclassified drug; promoter region; genetics; mutation; nonhuman; mass spectrometry; mouse; metabolism; gene; protein bcl 2; neoplasm proteins; animal experiment; animal model; pathology; dasatinib; tumor marker; carcinogenesis; tumor protein; lymphoma; cell migration; lymphoproliferative disease; lymphoma, large b-cell, diffuse; bone marrow transplantation; cell adhesion; migration; murine model; genes, cdc; ketamine; crk associated substrate protein; crk-associated substrate protein; fibronectin; scaffold protein; actin filament; b lymphocyte receptor; diffuse large b cell lymphoma; humans; human; article; drive; oncogenomics; xylazine; tmd8 cell line; btg1 protein, human; btg1 protein; bcar1 protein, human; diffuse large b-cell lymphoma cell line
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