TY - JOUR
T1 - Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma
AU - Rossi, Davide
AU - Deaglio, Silvia
AU - Dominguez-Sola, David
AU - Rasi, Silvia
AU - Vaisitti, Tiziana
AU - Agostinelli, Claudio
AU - Spina, Valeria
AU - Bruscaggin, Alessio
AU - Monti, Sara
AU - Cerri, Michaela
AU - Cresta, Stefania
AU - Fangazio, Marco
AU - Arcaini, Luca
AU - Lucioni, Marco
AU - Marasca, Roberto
AU - Thieblemont, Catherine
AU - Capello, Daniela
AU - Facchetti, Fabio
AU - Kwee, Ivo
AU - Pileri, Stefano A.
AU - Foà, Robin
AU - Bertoni, Francesco
AU - Dalla-Favera, Riccardo
AU - Pasqualucci, Laura
AU - Gaidano, Gianluca
PY - 2011/11/3
Y1 - 2011/11/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80855133512&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-06-359166
DO - 10.1182/blood-2011-06-359166
M3 - Article
SN - 0006-4971
VL - 118
SP - 4930
EP - 4934
JO - Blood
JF - Blood
IS - 18
ER -
