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Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.

Publication ,  Journal Article
Lenz, G; Davis, RE; Ngo, VN; Lam, L; George, TC; Wright, GW; Dave, SS; Zhao, H; Xu, W; Rosenwald, A; Ott, G; Muller-Hermelink, HK; Rimsza, LM ...
Published in: Science
March 21, 2008

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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Published In

Science

DOI

EISSN

1095-9203

Publication Date

March 21, 2008

Volume

319

Issue

5870

Start / End Page

1676 / 1679

Location

United States

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

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MLA
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Lenz, G., Davis, R. E., Ngo, V. N., Lam, L., George, T. C., Wright, G. W., … Staudt, L. M. (2008). Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science, 319(5870), 1676–1679. https://doi.org/10.1126/science.1153629
Lenz, Georg, R Eric Davis, Vu N. Ngo, Lloyd Lam, Thaddeus C. George, George W. Wright, Sandeep S. Dave, et al. “Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.Science 319, no. 5870 (March 21, 2008): 1676–79. https://doi.org/10.1126/science.1153629.
Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008 Mar 21;319(5870):1676–9.
Lenz, Georg, et al. “Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.Science, vol. 319, no. 5870, Mar. 2008, pp. 1676–79. Pubmed, doi:10.1126/science.1153629.
Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, Dave SS, Zhao H, Xu W, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Rimsza LM, Campo E, Jaffe ES, Delabie J, Smeland EB, Fisher RI, Chan WC, Staudt LM. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008 Mar 21;319(5870):1676–1679.
Journal cover image

Published In

Science

DOI

EISSN

1095-9203

Publication Date

March 21, 2008

Volume

319

Issue

5870

Start / End Page

1676 / 1679

Location

United States

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