Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

J.J. van Dongen; A.W. Langerak; M. Brüggemann; P.A. Evans; M. Hummel; F.L. Lavender; E. Delabesse; F. Davi; E. Schuuring; R. García-Sanz; J.H. van Krieken; J. Droese; D. González; C. Bastard; H.E. White; M. Spaargaren; M. González; A. Parreira; G.J. Morgan; M. Kneba; E.A. Macintyre; J.L Smith

doi:10.1038/sj.leu.2403202

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

J.J. van Dongen, A.W. Langerak, M. Brüggemann, P.A. Evans, M. Hummel, F.L. Lavender, E. Delabesse, F. Davi, E. Schuuring, R. García-Sanz, J.H. van Krieken, J. Droese, D. González, C. Bastard, H.E. White, M. Spaargaren, M. González, A. Parreira, G.J. Morgan, M. KnebaE.A. Macintyre, J.L Smith

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

2700 Citations (Scopus)

Abstract

In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

Original language	English
Pages (from-to)	2257-2317
Number of pages	61
Journal	Leukemia
Volume	17
Issue number	12
DOIs	https://doi.org/10.1038/sj.leu.2403202
Publication status	Published - Dec 2003

Keywords

Chromosome Aberrations
Clone Cells
DNA Primers
European Union
Gene Rearrangement, T-Lymphocyte
Humans
Immunoglobulins
Lymphoproliferative Disorders
Neoplasm, Residual
Polymerase Chain Reaction
Receptors, Antigen, T-Cell
Reference Standards
Reproducibility of Results

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http://www.ncbi.nlm.nih.gov/pubmed/14671650

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van Dongen, J. J., Langerak, A. W., Brüggemann, M., Evans, P. A., Hummel, M., Lavender, F. L., Delabesse, E., Davi, F., Schuuring, E., García-Sanz, R., van Krieken, J. H., Droese, J., González, D., Bastard, C., White, H. E., Spaargaren, M., González, M., Parreira, A., Morgan, G. J., ... Smith, J. L. (2003). Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia, 17(12), 2257-2317. https://doi.org/10.1038/sj.leu.2403202

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title = "Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.",

abstract = "In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.",

keywords = "Chromosome Aberrations, Clone Cells, DNA Primers, European Union, Gene Rearrangement, T-Lymphocyte, Humans, Immunoglobulins, Lymphoproliferative Disorders, Neoplasm, Residual, Polymerase Chain Reaction, Receptors, Antigen, T-Cell, Reference Standards, Reproducibility of Results",

author = "{van Dongen}, J.J. and A.W. Langerak and M. Br{\"u}ggemann and P.A. Evans and M. Hummel and F.L. Lavender and E. Delabesse and F. Davi and E. Schuuring and R. Garc{\'i}a-Sanz and {van Krieken}, J.H. and J. Droese and D. Gonz{\'a}lez and C. Bastard and H.E. White and M. Spaargaren and M. Gonz{\'a}lez and A. Parreira and G.J. Morgan and M. Kneba and E.A. Macintyre and J.L Smith",

year = "2003",

month = dec,

doi = "10.1038/sj.leu.2403202",

language = "English",

volume = "17",

pages = "2257--2317",

journal = "Leukemia",

issn = "0887-6924",

publisher = "Springer Nature",

number = "12",

}

van Dongen, JJ, Langerak, AW, Brüggemann, M, Evans, PA, Hummel, M, Lavender, FL, Delabesse, E, Davi, F, Schuuring, E, García-Sanz, R, van Krieken, JH, Droese, J, González, D, Bastard, C, White, HE, Spaargaren, M, González, M, Parreira, A, Morgan, GJ, Kneba, M, Macintyre, EA & Smith, JL 2003, 'Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.', Leukemia, vol. 17, no. 12, pp. 2257-2317. https://doi.org/10.1038/sj.leu.2403202

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. / van Dongen, J.J.; Langerak, A.W.; Brüggemann, M. et al.
In: Leukemia, Vol. 17, No. 12, 12.2003, p. 2257-2317.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936.

AU - van Dongen, J.J.

AU - Langerak, A.W.

AU - Brüggemann, M.

AU - Evans, P.A.

AU - Hummel, M.

AU - Lavender, F.L.

AU - Delabesse, E.

AU - Davi, F.

AU - Schuuring, E.

AU - García-Sanz, R.

AU - van Krieken, J.H.

AU - Droese, J.

AU - González, D.

AU - Bastard, C.

AU - White, H.E.

AU - Spaargaren, M.

AU - González, M.

AU - Parreira, A.

AU - Morgan, G.J.

AU - Kneba, M.

AU - Macintyre, E.A.

AU - Smith, J.L

PY - 2003/12

Y1 - 2003/12

N2 - In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

AB - In a European BIOMED-2 collaborative study, multiplex PCR assays have successfully been developed and standardized for the detection of clonally rearranged immunoglobulin (Ig) and T-cell receptor (TCR) genes and the chromosome aberrations t(11;14) and t(14;18). This has resulted in 107 different primers in only 18 multiplex PCR tubes: three VH-JH, two DH-JH, two Ig kappa (IGK), one Ig lambda (IGL), three TCR beta (TCRB), two TCR gamma (TCRG), one TCR delta (TCRD), three BCL1-Ig heavy chain (IGH), and one BCL2-IGH. The PCR products of Ig/TCR genes can be analyzed for clonality assessment by heteroduplex analysis or GeneScanning. The detection rate of clonal rearrangements using the BIOMED-2 primer sets is unprecedentedly high. This is mainly based on the complementarity of the various BIOMED-2 tubes. In particular, combined application of IGH (VH-JH and DH-JH) and IGK tubes can detect virtually all clonal B-cell proliferations, even in B-cell malignancies with high levels of somatic mutations. The contribution of IGL gene rearrangements seems limited. Combined usage of the TCRB and TCRG tubes detects virtually all clonal T-cell populations, whereas the TCRD tube has added value in case of TCRgammadelta(+) T-cell proliferations. The BIOMED-2 multiplex tubes can now be used for diagnostic clonality studies as well as for the identification of PCR targets suitable for the detection of minimal residual disease.

KW - Chromosome Aberrations

KW - Clone Cells

KW - DNA Primers

KW - European Union

KW - Gene Rearrangement, T-Lymphocyte

KW - Humans

KW - Immunoglobulins

KW - Lymphoproliferative Disorders

KW - Neoplasm, Residual

KW - Polymerase Chain Reaction

KW - Receptors, Antigen, T-Cell

KW - Reference Standards

KW - Reproducibility of Results

U2 - 10.1038/sj.leu.2403202

DO - 10.1038/sj.leu.2403202

M3 - Article

SN - 0887-6924

VL - 17

SP - 2257

EP - 2317

JO - Leukemia

JF - Leukemia

IS - 12

ER -

van Dongen JJ, Langerak AW, Brüggemann M, Evans PA, Hummel M, Lavender FL et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003 Dec;17(12):2257-2317. doi: 10.1038/sj.leu.2403202