Detail Oncogenic CARD11 Mutations in Human Diffuse Large B Cell Lymphoma   Oleh:  Lenz, Georg ; Davis, R. Eric ; Lam, Lloyd ; George, Thaddeus C. Jenis: Article from Bulletin/Magazine Dalam koleksi: SCIENCE (keterangan: ada di Proquest) vol. 319 no. 5870 (Mar. 2008), page 1676-1678. Topik: Oncogenic CARD11 Mutations; Human Diffuse Large B Cell Lymphoma Ketersediaan Perpustakaan FK Nomor Panggil: S01.K.2008.03 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada     Lihat Detail Induk Isi artikel 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–{kappa}B (NF-{kappa}B) signaling pathway. In normal B cells, antigen receptor–induced NF-{kappa}B 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-{kappa}B activation and enhanced NF-{kappa}B 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. Opini Anda Klik untuk menuliskan opini Anda tentang koleksi ini! Kembali

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