Oncogenic CARD11 mutations in human diffuse large B cell lymphoma |
| |
Authors: | Lenz Georg Davis R Eric Ngo Vu N Lam Lloyd George Thaddeus C Wright George W Dave Sandeep S Zhao Hong Xu Weihong Rosenwald Andreas Ott German Muller-Hermelink Hans Konrad Gascoyne Randy D Connors Joseph M Rimsza Lisa M Campo Elias Jaffe Elaine S Delabie Jan Smeland Erlend B Fisher Richard I Chan Wing C Staudt Louis M |
| |
Institution: | Metabolism Branch, Division of Cancer Treatment and Diagnosis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|