Splenic marginal zone lymphoma (SMZL) is one of few B-cell lymphoma types that remain orphan of molecular lesions in cancer related genes. Detection of active NF-κB signaling in 14/24 (58\%) SMZL prompted the investigation of NF-κB molecular alterations in 101 SMZL. Mutations and copy number abnormalities of NF-κB genes occurred in 36/101 (36\%) SMZL, and targeted both canonical (TNFAIP3 and IKBKB) and non-canonical (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 was recurrently due to somatic mutations disrupting the same RING domain that in extranodal marginal zone lymphoma is removed by the t(11;18), pointing 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 over 30\% SMZL, and offer a suitable target for NF-κB therapeutic targeting in this lymphoma.

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

DEAGLIO, Silvia;VAISITTI, TIZIANA;
2011

Abstract

Splenic marginal zone lymphoma (SMZL) is one of few B-cell lymphoma types that remain orphan of molecular lesions in cancer related genes. Detection of active NF-κB signaling in 14/24 (58\%) SMZL prompted the investigation of NF-κB molecular alterations in 101 SMZL. Mutations and copy number abnormalities of NF-κB genes occurred in 36/101 (36\%) SMZL, and targeted both canonical (TNFAIP3 and IKBKB) and non-canonical (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 was recurrently due to somatic mutations disrupting the same RING domain that in extranodal marginal zone lymphoma is removed by the t(11;18), pointing 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 over 30\% SMZL, and offer a suitable target for NF-κB therapeutic targeting in this lymphoma.
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http://bloodjournal.hematologylibrary.org/content/early/2011/08/30/blood-2011-06-359166.full.pdf+html
http://dx.doi.org/10.1182/blood-2011-06-359166
BIRC3; NF-κB pathway; splenic marginal zone lymphoma; mutations; copy number abnormalities
Rossi D; Deaglio S; Dominguez-Sola D; Rasi S; Vaisitti T; Agostinelli C; Spina V; Bruscaggin A; Monti S; Cerri M; Cresta S; Fangazio M; Arcaini L; Lucioni M; Marasca R; Thieblemont C; Capello D; Facchetti F; Kwee I; Pileri SA; Foà R; Bertoni F; Dalla-Favera R; Pasqualucci L; Gaidano G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/91359
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