
Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.
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.
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Related Subject Headings
- Sequence Analysis, DNA
- Receptors, Antigen, B-Cell
- Protein Structure, Tertiary
- Oncogenes
- NF-kappa B
- Mutation, Missense
- Molecular Sequence Data
- Lymphoma, Large B-Cell, Diffuse
- Jurkat Cells
- I-kappa B Kinase
Citation

Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Sequence Analysis, DNA
- Receptors, Antigen, B-Cell
- Protein Structure, Tertiary
- Oncogenes
- NF-kappa B
- Mutation, Missense
- Molecular Sequence Data
- Lymphoma, Large B-Cell, Diffuse
- Jurkat Cells
- I-kappa B Kinase