title: Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.
abstract: Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.
authors.affiliation: Haematological Malignancy Diagnostic Service, The General Infirmary at Leeds, Leeds, UK.
authors.forename: P A S
authors.initials: PA
authors.lastname: Evans
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authors.forename: P J T A
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authors.lastname: Groenen
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authors.lastname: Berger
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authors.lastname: Garcia
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authors.lastname: van Krieken
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authors.lastname: Pals
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authors.lastname: Kluin
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authors.lastname: Spaargaren
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authors.lastname: Boone
authors.forename: D
authors.initials: D
authors.lastname: González
authors.forename: B
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authors.lastname: Martinez
authors.forename: R
authors.initials: R
authors.lastname: Villuendas
authors.forename: P
authors.initials: P
authors.lastname: Gameiro
authors.forename: T C
authors.initials: TC
authors.lastname: Diss
authors.forename: K
authors.initials: K
authors.lastname: Mills
authors.forename: G J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: G I
authors.initials: GI
authors.lastname: Carter
authors.forename: B J
authors.initials: BJ
authors.lastname: Milner
authors.forename: D
authors.initials: D
authors.lastname: Pearson
authors.forename: M
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authors.lastname: Hummel
authors.forename: W
authors.initials: W
authors.lastname: Jung
authors.forename: M
authors.initials: M
authors.lastname: Ott
authors.forename: D
authors.initials: D
authors.lastname: Canioni
authors.forename: K
authors.initials: K
authors.lastname: Beldjord
authors.forename: C
authors.initials: C
authors.lastname: Bastard
authors.forename: M H
authors.initials: MH
authors.lastname: Delfau-Larue
authors.forename: J J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: T J
authors.initials: TJ
authors.lastname: Molina
authors.forename: J
authors.initials: J
authors.lastname: Cabeçadas
mesh_terms: D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D005838:Genotype; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015448:Leukemia, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction / Q000379:methods*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains; D011948:Receptors, Antigen, T-Cell