{"doi":"10.1126/sciadv.aay5872","title":"TET2 deficiency reprograms the germinal center B cell epigenome and silences genes linked to lymphomagenesis","abstract":"The TET2 DNA hydroxymethyltransferase is frequently disrupted by somatic mutations in diffuse large B cell lymphomas (DLBCLs), a tumor that originates from germinal center (GC) B cells. Here, we show that TET2 deficiency leads to DNA hypermethylation of regulatory elements in GC B cells, associated with silencing of the respective genes. This hypermethylation affects the binding of transcription factors including those involved in exit from the GC reaction and involves pathways such as B cell receptor, antigen presentation, CD40, and others. Normal GC B cells manifest a typical hypomethylation signature, which is caused by AID, the enzyme that mediates somatic hypermutation. However, AID-induced demethylation is markedly impaired in TET2-deficient GC B cells, suggesting that AID epigenetic effects are partially dependent on TET2. Last, we find that TET2 mutant DLBCLs also manifest the aberrant TET2-deficient GC DNA methylation signature, suggesting that this epigenetic pattern is maintained during and contributes to lymphomagenesis.","journal":"Science Advances","year":2020,"id":66634,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":239996,"name":"Xiaowen Chen","orcid":"0000-0002-5025-3423","position":1,"is_corresponding":false},{"id":353180,"name":"Pilar M. Domínguez","orcid":"0000-0002-5775-4351","position":2,"is_corresponding":false},{"id":353181,"name":"Hussein Ghamlouch","orcid":"0000-0002-2932-1081","position":3,"is_corresponding":false},{"id":353182,"name":"Saïd Aoufouchi","orcid":"0000-0001-6547-2664","position":4,"is_corresponding":false},{"id":318326,"name":"Olivier Bernard","orcid":"0000-0002-0463-9747","position":5,"is_corresponding":false},{"id":237422,"name":"Ari Melnick","orcid":"0000-0002-8074-2287","position":6,"is_corresponding":false},{"id":239997,"name":"Sheng Li","orcid":"0000-0002-9543-6274","position":7,"is_corresponding":false},{"id":342938,"name":"Wojciech Rosikiewicz","orcid":"0000-0001-7031-3430","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-18T21:14:50.590588Z","pmid":"32596441","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}