Alteration of BIRC3 and multiple other NF-κB pathway genes in splenic marginal zone lymphoma

Davide Rossi, Silvia Deaglio, David Dominguez-Sola, Silvia Rasi, Tiziana Vaisitti, Claudio Agostinelli, Valeria Spina, Alessio Bruscaggin, Sara Monti, Michaela Cerri, Stefania Cresta, Marco Fangazio, Luca Arcaini, Marco Lucioni, Roberto Marasca, Catherine Thieblemont, Daniela Capello, Fabio Facchetti, Ivo Kwee, Stefano A. PileriRobin Foà, Francesco Bertoni, Riccardo Dalla-Favera, Laura Pasqualucci, Gianluca Gaidano

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)4930-4934
Number of pages5
Issue number18
Publication statusPublished - Nov 3 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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