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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5870
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pubmed:dateCreated |
2008-3-21
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pubmed:abstractText |
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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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1095-9203
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pubmed:author |
pubmed-author:ChanWing CWC,
pubmed-author:ConnorsJoseph MJM,
pubmed-author:DaveSandeep SSS,
pubmed-author:DavisR EricRE,
pubmed-author:DelabieJanJ,
pubmed-author:FisherRichard IRI,
pubmed-author:GascoyneRandy DRD,
pubmed-author:GeorgeThaddeus CTC,
pubmed-author:JaffeElaine SES,
pubmed-author:KochM FMF,
pubmed-author:LamLloydL,
pubmed-author:LenzGeorgG,
pubmed-author:Muller-HermelinkHans KonradHK,
pubmed-author:NgoVu NVN,
pubmed-author:OttGermanG,
pubmed-author:RimszaLisa MLM,
pubmed-author:RosenwaldAndreasA,
pubmed-author:SmelandErlend BEB,
pubmed-author:StaudtLouis MLM,
pubmed-author:WrightGeorge WGW,
pubmed-author:XuWeihongW,
pubmed-author:ZhaoHongH
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pubmed:issnType |
Electronic
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pubmed:day |
21
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pubmed:volume |
319
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1676-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18323416-Amino Acid Sequence,
pubmed-meshheading:18323416-Apoptosis Regulatory Proteins,
pubmed-meshheading:18323416-CARD Signaling Adaptor Proteins,
pubmed-meshheading:18323416-Cell Line, Tumor,
pubmed-meshheading:18323416-Cytoplasm,
pubmed-meshheading:18323416-Guanylate Cyclase,
pubmed-meshheading:18323416-Humans,
pubmed-meshheading:18323416-I-kappa B Kinase,
pubmed-meshheading:18323416-Jurkat Cells,
pubmed-meshheading:18323416-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:18323416-Molecular Sequence Data,
pubmed-meshheading:18323416-Mutation, Missense,
pubmed-meshheading:18323416-NF-kappa B,
pubmed-meshheading:18323416-Oncogenes,
pubmed-meshheading:18323416-Protein Structure, Tertiary,
pubmed-meshheading:18323416-Receptors, Antigen, B-Cell,
pubmed-meshheading:18323416-Sequence Analysis, DNA
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pubmed:year |
2008
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pubmed:articleTitle |
Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.
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pubmed:affiliation |
Metabolism Branch, Division of Cancer Treatment and Diagnosis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
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