The NF-κB negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas

Urban Novak, Andrea Rinaldi, Ivo Kwee, Subhadra V. Nandula, Paola M V Rancoita, Mara Compagno, Michaela Cerri, Davide Rossi, Vundavalli V. Murty, Emanuele Zucca, Gianluca Gaidano, Riccardo Dalla-Favera, Laura Pasqualucci, Govind Bhagat, Francesco Bertoni

Research output: Contribution to journalArticlepeer-review

Abstract

Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-κB, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal MZL (EMZL), nodal MZL (NMZL), and splenic MZL (SMZL). Inactivating mutations encoding truncated A20 proteins were identified in 6 (19%) of 32 MZLs, including 2 (18%) of 11 EMZLs, 3 (33%) of 9 NMZLs, and 1 (8%) of 12 SMZLs. Two additional unmutated nonsplenic MZLs also showed monoallelic or biallelic A20 deletions by fluorescent in situ hybridization (FISH) and/or SNP-arrays. Thus, A20 inactivation by either somatic mutation and/or deletion represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-κB activation.

Original languageEnglish
Pages (from-to)4918-4921
Number of pages4
JournalBlood
Volume113
Issue number20
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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