ArticleThe Journal of experimental medicine2009
TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 218 papers, 1 of them a synthesis that pooled it.
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Who cites it
218 citing papers in PubMed, 1 synthesis or guideline pooled it, 471 citations in OpenAlex.
- Genome-wide association study implicates immune dysfunction in the development of Hodgkin lymphoma.Blood · 2018Pooled it
- STAT3 mutations in natural killer cells are associated with cytopenia in patients with chronic lymphoproliferative disorder of natural killer cells.International journal of hematology · 2019Trial
- Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjogren's syndrome.Blood · 2013Trial
- Immune checkpoint therapy in pediatric and adolescent lymphomas.Haematologica · 2026Review
- Genetic mechanisms of mitotic error in 840,853 blood genomes.medRxiv : the preprint server for health sciences · 2026Article
- The Epigenetic Architecture of Classical Hodgkin Lymphoma: Lineage Erasure, Immune Escape, and Therapeutic Reprogramming.Medicina (Kaunas, Lithuania) · 2026Review
- Genetic Variations inGenes · 2026Article
- Autosomal recessive A20 zinc finger 7 mutation is associated with early-onset lupus-like disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Revealing the promising therapeutic targets and prognostic markers of primary mediastinal large B-cell lymphoma.Discover oncology · 2026Review
- Targeted deep sequencing identifies mosaicism in patients with immune dysregulation.The Journal of allergy and clinical immunology · 2026Article
- Hodgkin Reed-Sternberg Cells of Classic Hodgkin Lymphoma: Morphology, Phenotype, Genotype, and Cell of Origin.Cancers · 2026Review
- Transcriptome sequencing of Hodgkin lymphoma Hodgkin and Reed-Sternberg cells reveals escape from NK cell recognition and an unfolded protein response.Blood cancer journal · 2026Article
- A20 restriction of nitric oxide production restores macrophage bioenergetic balance.bioRxiv : the preprint server for biology · 2025Article
- Article
- TP53 mutations and TET2 deficiency cooperate to drive leukemogenesis and establish an immunosuppressive environment.The Journal of clinical investigation · 2025Article
- The Role of A20 in Cancer: Friend or Foe?Cells · 2025Review
- Research landmarks on the 60th anniversary of Epstein-Barr virus.Science China. Life sciences · 2025Review
- Combination adjuvant improves influenza virus immunity by downregulation of immune homeostasis genes in lymphocytes.ImmunoHorizons · 2025Article
- B Cell Differentiation and the Origin and Pathogenesis of Human B Cell Lymphomas.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Somatic mutations in autoinflammatory and autoimmune disease.Nature reviews. Rheumatology · 2024Review
158 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proliferation and survival of Hodgkin and Reed/Sternberg (HRS) cells, the malignant cells of classical Hodgkin lymphoma (cHL), are dependent on constitutive activation of nuclear factor kappaB (NF-kappaB). NF-kappaB activation through various stimuli is negatively regulated by the zinc finger protein A20. To determine whether A20 contributes to the pathogenesis of cHL, we sequenced TNFAIP3, encoding A20, in HL cell lines and laser-microdissected HRS cells from cHL biopsies. We detected somatic mutations in 16 out of 36 cHLs (44%), including missense mutations in 2 out of 16 Epstein-Barr virus-positive (EBV(+)) cHLs and a missense mutation, nonsense mutations, and frameshift-causing insertions or deletions in 14 out of 20 EBV(-) cHLs. In most mutated cases, both TNFAIP3 alleles were inactivated, including frequent chromosomal deletions of TNFAIP3. Reconstitution of wild-type TNFAIP3 in A20-deficient cHL cell lines revealed a significant decrease in transcripts of selected NF-kappaB target genes and caused cytotoxicity. Extending the mutation analysis to primary mediastinal B cell lymphoma (PMBL), another lymphoma with constitutive NF-kappaB activity, revealed destructive mutations in 5 out of 14 PMBLs (36%). This report identifies TNFAIP3 (A20), a key regulator of NF-kappaB activity, as a novel tumor suppressor gene in cHL and PMBL. The significantly higher frequency of TNFAIP3 mutations in EBV(-) than EBV(+) cHL suggests complementing functions of TNFAIP3 inactivation and EBV infection in cHL pathogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.