Recurrent alterations of TNFAIP3 (A20) in T-cell large granular lymphocytic leukemia

Int J Cancer. 2016 Jan 1;138(1):121-4. doi: 10.1002/ijc.29697. Epub 2015 Jul 30.

Abstract

The pathogenesis of T-cell large granular lymphocytic leukemia (T-LGL) is poorly understood, as STAT3 mutations are the only known frequent genetic lesions. Here, we identified non-synonymous alterations in the TNFAIP3 tumor suppressor gene in 3 of 39 T-LGL. In two cases these were somatic mutations, in one case the somatic origin was likely. A further case harbored a SNP that is a known risk allele for autoimmune diseases and B cell lymphomas. Thus, TNFAIP3 mutations represent recurrent genetic lesions in T-LGL that affect about 8% of cases, likely contributing to deregulated NF-κB activity in this leukemia.

Keywords: NF-κB; STAT3; T-LGL; TNFAIP3; tumor suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • DNA Copy Number Variations
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Exons
  • Genetic Variation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Leukemia, Large Granular Lymphocytic / genetics*
  • Leukemia, Large Granular Lymphocytic / metabolism
  • Leukemia, Large Granular Lymphocytic / pathology
  • Mutation
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Polymorphism, Single Nucleotide
  • STAT3 Transcription Factor / genetics
  • Sequence Analysis, DNA
  • Tumor Necrosis Factor alpha-Induced Protein 3

Substances

  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • STAT3 Transcription Factor
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3