{"entity":{"id":"bcl2-rearrangement","kind":"biomarker","name":"BCL2 rearrangement, t(14;18)","aka":["t(14;18)","IGH::BCL2","BCL2 translocation","BCL2 break-apart FISH","bcl-2 rearrangement"],"tldr":"A swap of DNA that puts the survival gene BCL2 next to an antibody gene, so the cell makes far too much of a protein that stops it dying. It is the founding event of most follicular lymphomas and it happens in the bone marrow, often years before anything is wrong.","summary":"The t(14;18)(q32;q21) translocation joins BCL2 on chromosome 18 to the immunoglobulin heavy-chain locus on chromosome 14, so the anti-apoptotic protein is driven by the enhancer that should be driving antibody production. Sequencing the junctions showed that the breakpoints sit close to the 5' end of the JH segment, carry extraneous N-region nucleotides and lie beside signal-like sequences on chromosome 18, which identifies the translocation as a mistake by the VDJ recombinase at the pre-B-cell stage rather than a late event in a lymphoma (Tsujimoto 1985).\n\nIt is present in the large majority of follicular lymphomas and in 13.5% of 442 unselected diffuse large B-cell lymphomas in the RICOVER cohort, where BCL2 protein was expressed in 79.6% of tumours, far more often than the gene was rearranged (Horn 2013). A cell carrying the translocation can be found in the blood of healthy people, so the result on its own is not a diagnosis.","asOf":"2026-09-30","links":[{"label":"Tsujimoto et al., Science 1985: the t(14;18) translocation results from a mistake in VDJ joining","url":"https://doi.org/10.1126/science.3929382"},{"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"}],"tags":["biomarker","lymphoma"],"related":["double-hit-rearrangement","myc-bcl2-double-expressor"],"cancers":["follicular-lymphoma","dlbcl","non-hodgkin-lymphoma"],"sections":[],"technologies":["cytogenetics-fish","histopathology-ihc"],"targets":["bcl2"],"drugs":["venetoclax"],"companies":[],"institutions":[],"pathways":["apoptosis-bcl2","germinal-centre-reaction"],"terms":["fish","cytogenetics","lymphoma-bio-germinal-centre"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"bcl2","measurement":"fish-ratio","scoringRule":{"text":"A break at the BCL2 locus on interphase fluorescence in situ hybridisation, reported as rearranged or not rearranged, usually with a break-apart probe; a dual-fusion probe additionally confirms the immunoglobulin partner. The result is read alongside MYC and BCL6, because the combination rather than BCL2 alone defines the high-grade entity.","quote":"Rearrangements of MYC, BCL2, and BCL6 were detected in 8.8%, 13.5%, and 28.7%, respectively.","source":"https://doi.org/10.1182/blood-2012-06-435842","sourceLabel":"Horn et al., Blood 2013"},"thresholds":[],"definedBy":{"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"},"tests":[],"assays":[],"companionDiagnostics":[],"forPatient":"On its own this result helps name the lymphoma rather than choose the treatment. It becomes important when it appears together with a MYC rearrangement, which is a different and more aggressive diagnosis and usually means a stronger regimen."},"route":"/biomarkers/bcl2-rearrangement/","neighbours":{"biomarker":[{"id":"bcl2-g101v","kind":"biomarker","name":"BCL2 G101V and the other venetoclax binding-site mutations","route":"/biomarkers/bcl2-g101v/"},{"id":"myc-bcl2-double-expressor","kind":"biomarker","name":"Double expressor: MYC and BCL2 protein together by immunohistochemistry","route":"/biomarkers/myc-bcl2-double-expressor/"},{"id":"double-hit-rearrangement","kind":"biomarker","name":"Double-hit and triple-hit: MYC with BCL2 and BCL6 rearrangement","route":"/biomarkers/double-hit-rearrangement/"},{"id":"ezh2-y646-mutation","kind":"biomarker","name":"EZH2 gain-of-function mutation (Tyr646, originally Tyr641)","route":"/biomarkers/ezh2-y646-mutation/"}],"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"}],"technology":[{"id":"cytogenetics-fish","kind":"technology","name":"Cytogenetics and FISH","route":"/technologies/cytogenetics-fish/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"bcl2","kind":"target","name":"BCL-2","route":"/targets/bcl2/"}],"drug":[{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"}],"pathway":[{"id":"apoptosis-bcl2","kind":"pathway","name":"Intrinsic apoptosis (BCL-2 family)","route":"/pathways/apoptosis-bcl2/"},{"id":"germinal-centre-reaction","kind":"pathway","name":"The germinal centre reaction","route":"/pathways/germinal-centre-reaction/"}],"term":[{"id":"cytogenetics","kind":"term","name":"Cytogenetics and karyotype","route":"/terms/cytogenetics/"},{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"lymphoma-bio-germinal-centre","kind":"term","name":"The germinal centre: why lymphoma starts where antibodies are made","route":"/terms/lymphoma-bio-germinal-centre/"}]}}