{"entity":{"id":"clonality-testing","kind":"technology","name":"Immunoglobulin and T-cell receptor clonality testing","aka":["IGH clonality","TCR clonality","BIOMED-2","EuroClonality","gene rearrangement study","B-cell clonality","T-cell clonality"],"tldr":"A test that asks whether a group of lymphocytes is one family descended from a single cell, or a crowd of unrelated ones. Cancer is one family. It is used when the appearance under the microscope is not enough to decide.","summary":"Every B cell and T cell rearranges its antigen receptor genes into a sequence unique to itself, so the length and sequence of that rearrangement is a fingerprint for the cell and all its descendants. A reactive lymph node contains thousands of different rearrangements and gives a smooth, polyclonal distribution; a lymphoma contains one, repeated, and gives a single peak.\n\nThe European BIOMED-2 collaboration standardised the assay into 107 primers in 18 multiplex tubes covering the immunoglobulin heavy chain in two configurations, the kappa and lambda light chains, the T-cell receptor beta, gamma and delta loci, and the BCL1-IGH and BCL2-IGH translocations, read by heteroduplex analysis or fragment sizing. The EuroClonality-NGS successor sequences the amplicons instead of sizing them, which both improves resolution and produces a patient-specific sequence that can be followed afterwards as a residual disease marker.\n\nThe assay is most often ordered where morphology and immunohistochemistry disagree or where the sample is small: a skin biopsy in suspected cutaneous T-cell lymphoma, a gastric biopsy in suspected MALT lymphoma, a marrow with an ambiguous infiltrate, or a lymph node with an atypical but not clearly malignant population.","asOf":"2026-09-30","links":[{"label":"van Dongen et al., Leukemia 2003: BIOMED-2 multiplex PCR for clonal immunoglobulin and T-cell receptor rearrangements","url":"https://doi.org/10.1038/sj.leu.2403202"}],"tags":["diagnostics","lymphoma"],"related":[],"cancers":["non-hodgkin-lymphoma","cutaneous-t-cell-lymphoma","sezary-syndrome","malt-lymphoma","marginal-zone-lymphoma","peripheral-t-cell-lymphoma","follicular-lymphoma","dlbcl"],"sections":[],"technologies":["ngs-mrd-clonoseq","histopathology-ihc","flow-cytometry-mrd","mrd-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ngs","mrd","lymphoma-bio-germinal-centre"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Multiplex PCR, or targeted sequencing, across the V, D and J segments of the immunoglobulin and T-cell receptor loci. A clonal population gives amplicons of one length and sequence; a polyclonal population gives a Gaussian spread of lengths. The output is a pattern, not a diagnosis.","strengths":["Works on tiny and on fixed samples, including paraffin blocks and skin punch biopsies, where flow cytometry cannot be done","Combined immunoglobulin heavy-chain and kappa tubes detect virtually all clonal B-cell proliferations, even where somatic hypermutation has altered the primer binding sites, and combined T-cell receptor beta and gamma tubes detect virtually all clonal T-cell populations (van Dongen 2003)","The sequence it finds can be reused as a patient-specific residual disease marker afterwards","Standardised across European laboratories, so a result travels between centres"],"limitations":["Clonality is not malignancy. Clonal populations occur in reactive and autoimmune conditions, in skin, in coeliac disease and in older people, and reporting a clonal result as a diagnosis is the commonest way this test does harm","A polyclonal result does not exclude lymphoma, particularly where the malignant cells are a small minority of the sample, as in classical Hodgkin lymphoma","Heavily mutated immunoglobulin genes can defeat primer binding, which is why the complementary tubes exist","It says nothing about which lymphoma it is"],"since":2003},"route":"/technologies/clonality-testing/","neighbours":{"cancer":[{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"malt-lymphoma","kind":"cancer","name":"Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)","route":"/cancers/malt-lymphoma/"},{"id":"follicular-lymphoma","kind":"cancer","name":"Follicular lymphoma","route":"/cancers/follicular-lymphoma/"},{"id":"mantle-cell-lymphoma","kind":"cancer","name":"Mantle cell lymphoma","route":"/cancers/mantle-cell-lymphoma/"},{"id":"marginal-zone-lymphoma","kind":"cancer","name":"Marginal zone lymphoma","route":"/cancers/marginal-zone-lymphoma/"},{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"},{"id":"richter-transformation-cll","kind":"cancer","name":"Richter transformation of chronic lymphocytic leukaemia","route":"/cancers/richter-transformation-cll/"},{"id":"sezary-syndrome","kind":"cancer","name":"Sezary syndrome","route":"/cancers/sezary-syndrome/"},{"id":"waldenstrom","kind":"cancer","name":"Waldenström macroglobulinaemia","route":"/cancers/waldenstrom/"}],"technology":[{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"},{"id":"flow-cytometry-mrd","kind":"technology","name":"Multiparameter flow cytometry MRD","route":"/technologies/flow-cytometry-mrd/"},{"id":"ngs-mrd-clonoseq","kind":"technology","name":"NGS-based MRD (clonoSEQ and molecular MRD)","route":"/technologies/ngs-mrd-clonoseq/"}],"term":[{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"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":"ig-tcr-clonality","kind":"biomarker","name":"Immunoglobulin and T-cell receptor clonality","route":"/biomarkers/ig-tcr-clonality/"}]}}