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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.
Hong Zhao
Weihong Xu
Rosenwald, Andreas
Ott, German
Muuer-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.
Source :
Science. 3/21/2008, Vol. 319 Issue 5870, p1676-1678. 3p. 3 Graphs.
Publication Year :
2008

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-κB (NF-κB) signaling pathway. In normal B cells, antigen receptor-induced NF-κB 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-κB activation and enhanced NF-κB activity upon antigen receptor stimulation. These results demonstrate that CARD11 is a bona fide oncogene in DLBCL providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00368075
Volume :
319
Issue :
5870
Database :
Academic Search Index
Journal :
Science
Publication Type :
Academic Journal
Accession number :
31775874
Full Text :
https://doi.org/10.1126/science.1153629