2008/03/06 by Georg Lenz, R. Eric Davis, Vu N. Ngo +19 · 4 citations
Medicine · Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Lymphoma Diagnosis and Treatment #NF-κB Signaling Pathways #T-cell and Retrovirus Studies #Diffuse large B-cell lymphoma #Cancer research #Lymphoma #BCL10 #Biology #Carcinogenesis #Missense mutation #Mutation #Gene #Genetics #Immunology
paper · doi:10.1126/science.1153629
openalex publication_date 2008/03/06 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/01
Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant cells is dependent on constitutive activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway. In normal B cells, antigen receptor-induced NF-kappaB activation requires CARD11, a cytoplasmic scaffolding protein. To determine whether CARD11 contributes to tumorigenesis, we sequenced the CARD11 gene in human DLBCL tumors. We detected missense mutations in 7 of 73 ABC DLBCL biopsies (9.6%), all within exons encoding the coiled-coil domain. Experimental introduction of CARD11 coiled-coil domain mutants into lymphoma cell lines resulted in constitutive NF-kappaB activation and enhanced NF-kappaB activity upon antigen receptor stimulation. These results demonstrate that CARD11 is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.