{"entity":{"id":"bcl6","kind":"target","name":"BCL6","aka":["BCL6 transcription repressor","B-cell lymphoma 6 protein","ZBTB27","LAZ3","BCL5","BCL6A","ZNF51"],"tldr":"BCL6 (B-cell lymphoma 6 protein) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver, a tumour suppressor, a biomarker and a fusion partner, and clinical evidence ties its variants to diagnosis, prognosis or drug response. Tied to Non-Hodgkin lymphoma, Lung cancer, Myeloproliferative neoplasms and 3 more.","summary":"Transcriptional repressor mainly required for germinal centre (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors.\n\nCIViC holds 2 clinical evidence items and 0 assertions across 2 variants. Open Targets scores its association with cancer at 0.63 (direct and indirect evidence; datatypes literature 0.99, animal model 0.29, genetic association 0.00, somatic mutation 0.98). IntOGen calls it a driver in 4 cohorts (2 activating, 2 loss-of-function), covering Diffuse Large B-Cell Lymphoma, NOS, Malignant Lymphoma.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:1001","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1001"},{"label":"UniProt P41182","url":"https://www.uniprot.org/uniprotkb/P41182/entry"},{"label":"NCBI Gene 604","url":"https://www.ncbi.nlm.nih.gov/gene/604"},{"label":"Ensembl ENSG00000113916","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000113916"},{"label":"Dalla-Favera et al., PNAS 1982: human c-myc lies in the chromosome 8 region translocated in Burkitt lymphoma","url":"https://doi.org/10.1073/pnas.79.24.7824"},{"label":"Horn et al., Blood 2013: MYC, BCL2 and BCL6 rearrangement and expression in 442 RICOVER patients","url":"https://doi.org/10.1182/blood-2012-06-435842"},{"label":"Johnson et al., J Clin Oncol 2012: concurrent MYC and BCL2 protein expression in diffuse large B-cell lymphoma treated with R-CHOP","url":"https://doi.org/10.1200/JCO.2011.41.0985"},{"label":"Alaggio et al., Leukemia 2022: the fifth edition of the WHO classification of haematolymphoid tumours, lymphoid neoplasms","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"Schmitz et al., N Engl J Med 2018: genetics and pathogenesis of diffuse large B-cell lymphoma (574 biopsies; MCD, BN2, N1, EZB)","url":"https://doi.org/10.1056/NEJMoa1801445"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["non-hodgkin-lymphoma","lung-cancer","myeloproliferative-neoplasms","colorectal","skin-cancer","dlbcl"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":["myc","transcription-addiction","epigenetic-reprogramming"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 2 cohorts; CIViC holds 2 clinical evidence items on its variants; UniProt disease notes describe a translocation or gene fusion involving the gene. Evidence tier \"clinical-evidence\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Lymphoma, MYC, and the double-hit and triple-hit definitions: MYC was mapped to 8q24, the region translocated to chromosome 2, 14 or 22 in Burkitt lymphoma cells, in 1982 (Dalla-Favera 1982); the partner is always an immunoglobulin locus, so the transcription factor is driven by the enhancer that should be driving antibody production. A double hit is a MYC rearrangement together with a BCL2 rearrangement, a triple hit adds BCL6. The two lesions are complementary rather than additive: MYC drives proliferation and would normally trigger apoptosis, and BCL2 removes that safeguard. Frequency: MYC rearrangement in 8.8% of 442 diffuse large B-cell lymphomas, BCL2 in 13.5% and BCL6 in 28.7% (Horn 2013). Protein overexpression is much commoner than rearrangement: MYC protein above the 40% threshold in 31.8% of the same cohort (Horn 2013), and in a separate 167-patient training cohort MYC protein in 29%, BCL2 protein in 44% and both together in 21%, against MYC translocation in only 11% (Johnson 2012). What it changes about treatment: The WHO fifth edition separates high-grade B-cell lymphoma with MYC and BCL2 rearrangements as its own entity (Alaggio 2022), and in practice a double hit moves most patients off R-CHOP onto a more intensive regimen, although the randomised evidence for doing so is thin. Double expression of the two proteins without rearrangement is prognostic, not a separate entity, and does not by itself change the regimen: in the trial cohort MYC protein predicted worse survival only when BCL2 protein was present too (Johnson 2012).","Lymphoma, BCL6 and the germinal-centre programme: BCL6 is the master transcriptional repressor of the germinal centre: it switches off the DNA-damage response and the differentiation programme so that a B cell can tolerate deliberate mutation of its own immunoglobulin genes. A lymphoma that keeps BCL6 on keeps a cell in a state where mutation is permitted and apoptosis is suppressed. The protein is normally switched off by acetylation, which is one reason CREBBP and EP300 loss matters here. Frequency: BCL6 rearrangement in 28.7% of 442 diffuse large B-cell lymphomas, the commonest of the three translocations (Horn 2013); BCL6 fusions with NOTCH2 mutations define the BN2 subtype (Schmitz 2018). What it changes about treatment: Nothing yet. There is no approved BCL6 inhibitor or degrader, and the group's prognosis in the genetic classification is comparatively favourable, which is a reason to study de-escalation rather than a reason to change treatment now."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"BCL6","role":["oncogene-driver","tumour-suppressor","biomarker","fusion-partner"],"evidenceTier":"clinical-evidence","sources":[{"label":"HGNC HGNC:1001","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1001","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P41182","url":"https://www.uniprot.org/uniprotkb/P41182/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene BCL6","url":"https://civicdb.org/features/566","note":"2 evidence items, 0 assertions, 2 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000113916","url":"https://platform.opentargets.org/target/ENSG00000113916/associations","note":"association with cancer (MONDO_0004992) 0.63; per-cancer scores at or above 0.5: colorectal cancer 0.52, diffuse large B-cell lymphoma 0.60, non-Hodgkin lymphoma 0.66, skin cancer 0.52, myeloproliferative neoplasm 0.53, lung cancer 0.53 (GraphQL API, CC0)"},{"label":"IntOGen BCL6","url":"https://www.intogen.org/search?gene=BCL6","note":"driver in 4 cohorts (Act 2, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: the catalogues call it an oncogene driver (IntOGen cohort analysis finds it activated more often than chance) and a tumour suppressor (IntOGen finds it knocked out more often than chance) and a fusion partner (UniProt records a translocation), so the direction differs between cohorts but the alteration is somatic either way; what a medicine would aim at or exploit is the altered form or its loss, absent from normal cells; no corpus medicine is aimed at it yet. HPA BCL6: RNA tissue enhanced (skeletal muscle 528 nTPM); blood lineage group enriched (granulocytes 270 nTPM, monocytes 77 nTPM); high antibody staining in 4 normal tissues; highest cancer staining lymphoma (2 of 12 high). Distribution: 5 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Lung cancer (all types), Myeloid neoplasms, Colorectal cancer, Skin cancer (all types)); Open Targets associates it with 1 specific cancer type at or above 0.5 (diffuse large B-cell lymphoma). (Rule 6 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"UniProt P41182","url":"https://www.uniprot.org/uniprotkb/P41182/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene BCL6","url":"https://civicdb.org/features/566","note":"2 evidence items, 0 assertions, 2 variants; diseases: Diffuse Large B-cell Lymphoma (GraphQL API, CC0)"},{"label":"IntOGen BCL6","url":"https://www.intogen.org/search?gene=BCL6","note":"driver in 4 cohorts (Act 2, LoF 2); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"},{"label":"Human Protein Atlas BCL6 tissue","url":"https://www.proteinatlas.org/ENSG00000113916-BCL6/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000113916 associations","url":"https://platform.opentargets.org/target/ENSG00000113916/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:1001","ensembl":"ENSG00000113916","uniprot":"P41182","entrez":"604","firstDescribed":1993,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Kerckaert J.-P. et al, Nat. Genet, 1993, \"LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/8220427/","biology":"Transcriptional repressor mainly required for germinal centre (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunoglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4(+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Location: Nucleus (UniProt). Locus 3q27.3 (HGNC).","whereFound":["Non-Hodgkin lymphoma: Open Targets association 0.66 with non-Hodgkin lymphoma (MONDO_0018908); IntOGen driver in 2 cohorts (MLYM)","Lung cancer: Open Targets association 0.53 with lung cancer (MONDO_0008903)","Myeloproliferative neoplasms: Open Targets association 0.53 with myeloproliferative neoplasm (MONDO_0020076)","Colorectal cancer: Open Targets association 0.52 with colorectal cancer (MONDO_0005575)","Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)","Diffuse large B-cell lymphoma: Open Targets association 0.60 with diffuse large B-cell lymphoma (MONDO_0018905); CIViC evidence names this disease"],"targetClass":"transcription","prevalence":[]},"route":"/targets/bcl6/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"}],"pathway":[{"id":"epigenetic-reprogramming","kind":"pathway","name":"Epigenetic reprogramming","route":"/pathways/epigenetic-reprogramming/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"germinal-centre-reaction","kind":"pathway","name":"The germinal centre reaction","route":"/pathways/germinal-centre-reaction/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"term":[{"id":"lymphoma-bio-cell-of-origin-in-practice","kind":"term","name":"Cell of origin in practice: Hans against expression profiling, and what it changes","route":"/terms/lymphoma-bio-cell-of-origin-in-practice/"},{"id":"double-hit-lymphoma","kind":"term","name":"Double-hit / high-grade B-cell lymphoma","route":"/terms/double-hit-lymphoma/"},{"id":"lymphoma-bio-lymphgen","kind":"term","name":"LymphGen and the genetic clusters of large B-cell lymphoma","route":"/terms/lymphoma-bio-lymphgen/"},{"id":"lymphoma-bio-germinal-centre","kind":"term","name":"The germinal centre: why lymphoma starts where antibodies are made","route":"/terms/lymphoma-bio-germinal-centre/"}],"biomarker":[{"id":"double-hit-rearrangement","kind":"biomarker","name":"Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement","route":"/biomarkers/double-hit-rearrangement/"}],"paper":[{"id":"paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020","kind":"paper","name":"A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications","route":"/key-papers/paper-wright-lymphgen-genetic-subtypes-dlbcl-cancer-cell-2020/"},{"id":"paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004","kind":"paper","name":"Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray","route":"/key-papers/paper-hans-immunohistochemistry-cell-of-origin-dlbcl-blood-2004/"},{"id":"paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018","kind":"paper","name":"Genetics and pathogenesis of diffuse large B-cell lymphoma","route":"/key-papers/paper-schmitz-genetics-pathogenesis-dlbcl-nejm-2018/"},{"id":"paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018","kind":"paper","name":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","route":"/key-papers/paper-chapuy-molecular-subtypes-dlbcl-nat-med-2018/"},{"id":"paper-rosenwald-molecular-profiling-dlbcl-nejm-2002","kind":"paper","name":"The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma","route":"/key-papers/paper-rosenwald-molecular-profiling-dlbcl-nejm-2002/"}],"roadmap":[{"id":"lymphoma-roadmap","kind":"roadmap","name":"Lymphoma roadmap: from a jaw tumour in Uganda and the first human cancer virus to gene-expression subtypes, PET-adapted chemotherapy, CAR-T cells, bispecific antibodies and the genetics-directed trials now recruiting","route":"/roadmaps/lymphoma-roadmap/"}]}}