Journal
BLOOD
Volume 118, Issue 18, Pages 4930-4934Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-06-359166
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Funding
- AIRC, Milan, Italy [10007]
- MIUR, Rome, Italy
- Ministero della Salute, Rome, Italy
- Novara-Associazione Italiana contro le Leucemie, Linfomi e Mielomi (AIL) Onlus, Novara, Italy
- Oncosuisse grant [OCS-02034-02-2007]
- Swiss National Science Foundation [205321-112430]
- Fondazione per la Ricerca e la Cura sui Linfomi, Lugano, Switzerland
- Computational Life Science/Ticino in rete
- Associazione Franca Capurro per Novara Onlus, Novara, Italy
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Splenic marginal zone lymphoma (SMZL) is one of the few B-cell lymphoma types that remain orphan of molecular lesions in cancer-related genes. Detection of active NF-kappa B signaling in 14 (58%) of 24 SMZLs prompted the investigation of NF-kappa B molecular alterations in 101 SMZLs. Mutations and copy number abnormalities of NF-kappa B genes occurred in 36 (36%) of 101 SMZLs and targeted both canonical (TNFAIP3 and IKBKB) and noncanonical (BIRC3, TRAF3, MAP3K14) NF-kappa B pathways. Most alterations were mutually exclusive, documenting the existence of multiple independent mechanisms affecting NF-kappa B in SMZL. BIRC3 inactivation in SMZL recurred because of somatic mutations that disrupted the same RING domain that in extranodal marginal zone lymphoma is removed by the t(11;18) translocation, which points to BIRC3 disruption as a common mechanism across marginal zone B-cell lymphomagenesis. Genetic lesions of NF-kappa B provide a molecular basis for the pathogenesis of more than 30% of SMZLs and offer a suitable target for NF-kappa B therapeutic approaches in this lymphoma. (Blood. 2011;118(18):4930-4934)
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