# Immunoglobulin and T-cell receptor clonality testing

Source: https://onco.cc/technologies/clonality-testing/  
OnCo record `clonality-testing` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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.

The 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.

## Fields

- Kind: Technology
- Last checked: 2026-09-30
- Also known as: IGH clonality; TCR clonality; BIOMED-2; EuroClonality; gene rearrangement study; B-cell clonality; T-cell clonality
- Tags: diagnostics; lymphoma
- 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.
- Since: 2003
- 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

## Sources

- van Dongen et al., Leukemia 2003: BIOMED-2 multiplex PCR for clonal immunoglobulin and T-cell receptor rearrangements: https://doi.org/10.1038/sj.leu.2403202

## Connected records

- cancers: [Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)](https://onco.cc/cancers/cutaneous-t-cell-lymphoma/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)](https://onco.cc/cancers/malt-lymphoma/), [Follicular lymphoma](https://onco.cc/cancers/follicular-lymphoma/), [Mantle cell lymphoma](https://onco.cc/cancers/mantle-cell-lymphoma/), [Marginal zone lymphoma](https://onco.cc/cancers/marginal-zone-lymphoma/), [Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)](https://onco.cc/cancers/angioimmunoblastic-t-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/), [Richter transformation of chronic lymphocytic leukaemia](https://onco.cc/cancers/richter-transformation-cll/), [Sezary syndrome](https://onco.cc/cancers/sezary-syndrome/), [Waldenström macroglobulinaemia](https://onco.cc/cancers/waldenstrom/)
- technologies: [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/), [Multiparameter flow cytometry MRD](https://onco.cc/technologies/flow-cytometry-mrd/), [NGS-based MRD (clonoSEQ and molecular MRD)](https://onco.cc/technologies/ngs-mrd-clonoseq/)
- terms: [Minimal / molecular residual disease (MRD)](https://onco.cc/terms/mrd/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [The germinal centre: why lymphoma starts where antibodies are made](https://onco.cc/terms/lymphoma-bio-germinal-centre/)
- biomarkers: [Immunoglobulin and T-cell receptor clonality](https://onco.cc/biomarkers/ig-tcr-clonality/)

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