title: Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma.
abstract: 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-κB signaling in 14 (58%) of 24 SMZLs prompted the investigation of NF-κB molecular alterations in 101 SMZLs. Mutations and copy number abnormalities of NF-κB genes occurred in 36 (36%) of 101 SMZLs and targeted both canonical (TNFAIP3 and IKBKB) and noncanonical (BIRC3, TRAF3, MAP3K14) NF-κB pathways. Most alterations were mutually exclusive, documenting the existence of multiple independent mechanisms affecting NF-κB 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-κB provide a molecular basis for the pathogenesis of more than 30% of SMZLs and offer a suitable target for NF-κB therapeutic approaches in this lymphoma.
authors: Division of Hematology, Department of Clinical and Experimental Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy. rossidav@med.unipmn.it
authors: Davide
authors: D
authors: Rossi
authors: Silvia
authors: S
authors: Deaglio
authors: David
authors: D
authors: Dominguez-Sola
authors: Silvia
authors: S
authors: Rasi
authors: Tiziana
authors: T
authors: Vaisitti
authors: Claudio
authors: C
authors: Agostinelli
authors: Valeria
authors: V
authors: Spina
authors: Alessio
authors: A
authors: Bruscaggin
authors: Sara
authors: S
authors: Monti
authors: Michaela
authors: M
authors: Cerri
authors: Stefania
authors: S
authors: Cresta
authors: Marco
authors: M
authors: Fangazio
authors: Luca
authors: L
authors: Arcaini
authors: Marco
authors: M
authors: Lucioni
authors: Roberto
authors: R
authors: Marasca
authors: Catherine
authors: C
authors: Thieblemont
authors: Daniela
authors: D
authors: Capello
authors: Fabio
authors: F
authors: Facchetti
authors: Ivo
authors: I
authors: Kwee
authors: Stefano A
authors: SA
authors: Pileri
authors: Robin
authors: R
authors: Foà
authors: Francesco
authors: F
authors: Bertoni
authors: Riccardo
authors: R
authors: Dalla-Favera
authors: Laura
authors: L
authors: Pasqualucci
authors: Gianluca
authors: G
authors: Gaidano
mesh_terms: D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D016022:Case-Control Studies; D016000:Cluster Analysis; D004252:DNA Mutational Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D046228:Microarray Analysis; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013160:Splenic Neoplasms / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases