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  • Biotechnical Methods Section BTS
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Biotechnical Methods Section (BTS)

Detection of illegitimate rearrangements within the immunoglobulin light chain loci in B cell malignancies using end sequenced probes

Leukemia volume 16, pages 2148–2155 (2002)Cite this article

Abstract

Translocations involving the immunoglobulin loci are recurring events of B cell oncogenesis. The majority of translocations involve the immunoglobulin heavy chain (IGH) locus, while a minor part involves the immunoglobulin light chain loci consisting of the kappa light chain (IGK) located at 2p11.2 and the lambda light chain (IGL) located at 22q11.2. We characterised BAC clones, spanning the IGK and IGL loci, for detection of illegitimate rearrangements by fluorescence in situ hybridisation (FISH). Within the IGL region we have identified six end sequenced probes (22M5, 1152K19, 2036J16, 3188M21, 3115E23 and 274M7) covering the variable (IGLV) cluster and two probes (165G5 and 31L9) covering the constant (IGLC) cluster. Within the IGK region four probes (969D7, 316G9, 122B6 and 2575M21) have been identified covering the variable (IGKV) cluster, and one probe (1021F11) covering the IGK constant (IGKC) cluster. A series of 24 cell lines of different origin have been analysed for the presence of translocations involving the immunoglobulin light chain loci by dual-colour FISH where the split of the variable cluster and the constant cluster indicated a translocation. Probes established in this study can be used for universal screening of illegitimate rearrangements within the immunoglobulin light chain loci in B cell malignancies.

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References

  1. Tonegawa S . Somatic generation of antibody diversity Nature 1983 302: 575–581

    Article  CAS  PubMed  Google Scholar 

  2. Matsuda F, Ishii K, Bourvanet P, Kuma K-I, Hayashida H, Miyata T, Honjo T . The complete nucleotide sequence of the human immunoglobulin heavy chain variable region locus J Exp Med 1998 11: 2151–2162

    Article  Google Scholar 

  3. Kawasaki K, Minoshima S, Nakato E, Shibuya K, Shintani A, Schmeits JL, Wang J, Shimizu N . One-megabase sequence analysis of the human immunoglobulin λ gene locus Genome Res 1997 7: 250–261

    Article  CAS  PubMed  Google Scholar 

  4. Kawasaki K, Minoshima S, Nakato E, Shibuya K, Shintani A, Shintani A, Asakawa S, Sasaki T, Klobeck HG, Combriato G, Zachau HG, Shimizu N . Evolutionary dynamics of the human immunoglobulin κ locus and the germline repertoire of the Vκ genes Eur J Immunol 2001 31: 1017–1028

    Article  CAS  PubMed  Google Scholar 

  5. Zachau HG . The immunoglobulin κ locus – or – what has been learned from looking closely at one-tenth of a percent of the human genome Gene 1993 135: 167–173

    Article  CAS  PubMed  Google Scholar 

  6. Ruiz M, Giudicelli V, Ginestoux C, Stoehr P, Robinson J, Bodmer J, Marsh SGE, Bontrop R, Lemaitre M, Lefranc G, Chaume D, Lefranc M-P . IMGT, the international ImMunoGeneTics database Nucleic Acids Res 2000 28: 219–221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Malcolm S, Barton P, Murphy C, Ferguson-Smith MA, Bentley DL, Rabbitts TH . Localisation of human immunoglobulin kappa light chain variable genes to the short arm of chromosome 2 by in situ hybridisation Proc Natl Acad Sci USA 1982 79: 4957–4961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rabbitts TH, Boehm T . Structural and functional chimerism results from chromosomal translocation in lymphoid tumors Adv Immunol 1991 50: 119–146

    Article  CAS  PubMed  Google Scholar 

  9. Willis TG, Dyer MJS . The role of immunoglobulin translocations in the pathogenesis of B-cell malignancies Blood 2000 96: 808–822

    CAS  PubMed  Google Scholar 

  10. Lenoir GM, O'Conor GT, Olweny CLM (eds). Burkitt's Lymphoma: A Human Cancer Model. IARC Scientific Publications No 60, International Agency for Research on Cancer: Lyon 1985

    Google Scholar 

  11. Komatsu H, Yoshida K, Seto M, Iida S, Aikawa T, Ueda R, Mikuni C . Overexpression of PRAD1 in a mantle zone lymphoma patient with a t(11;22)(q13;q11) translocation Br J Haematol 1993 85: 427–429

    Article  CAS  PubMed  Google Scholar 

  12. Poulsen TS, Silahtaroglu AN, Gisselø CG, Gaarsdal E, Rasmussen T, Tommerup N, Johnsen HE . Detection of illegitimate rearrangement within the immunoglobulin locus on 14q32.3 in B-cell malignancies using end sequenced probes Genes Chromosomes Cancer 2001 32: 265–274

    Article  CAS  PubMed  Google Scholar 

  13. Zhao S, Malek J, Mahairas G, Fu L, Nierman W, Venter JC, Adams MD . Human BAC ends quality assessment and sequence analyses Genomics 2000 63: 321–332

    Article  CAS  PubMed  Google Scholar 

  14. Erdel M, Hubalek M, Lingenhel A, Kofler K, Duba H-C, Utermann G . Counting the repetitive kringle-IV repeats in the gene encoding human apolipoprotein (a) by fibre-FISH Nat Genet 1999 21: 357–358

    Article  CAS  PubMed  Google Scholar 

  15. Lefranc M-P . IMGT, the international ImMunoGeneTics database Nucleic Acids Res 2001 29: 207–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cario G, Stadt UZ, Reiter A, Welte K, Sykora K-W . Variant translocations in sporadic Burkitt's lymphoma detected in fresh tumour material: analysis of three cases Br J Haematol 2000 110: 537–546

    Article  CAS  PubMed  Google Scholar 

  17. Yonetani N, Ueda C, Akasaka T, Nishikori M, Uchiyama T, Ohno H . Heterogeneous breakpoints on the immunoglobin genes are involved in fusion with the 5′ region of BCL2 in B-cell tumors Jpn J Cancer 2001 92: 933–940

    Article  CAS  Google Scholar 

  18. Weichhold GM, Ohnheiser R, Zachau HG . The human immunoglobulin (locus consists of two copies that are organised in opposite polarity Genomics 1993 16: 503–511

    Article  CAS  PubMed  Google Scholar 

  19. Drexler HG . The Leukemia–Lymphoma Cell Line, Facts Book Academic Press: London 2001

    Google Scholar 

  20. Gabrea A, Bergsagel PL, Chesi M, Shou Y, Kuehl WM . Insertion of excised IgH switch sequences causes overexpression of cyclin D1 in a myeloma tumor cell Mol Cell 1999 3: 119–123

    Article  CAS  PubMed  Google Scholar 

  21. http://www.gbf-braunschweig.de/DSMZ/dsmzhome.htm (DSMZ, Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH

  22. http://www.atcc.org/SearchCatalogs/CellBiology.cfm#newstrains (ATCC, American Type Culture Collection, Cell Biology)

  23. Drexler HG, MacLeod RAF, Dirks WG . Cross-contamination: HS-Sultan is not a myeloma but a Burkitt lymphoma cell line Blood 2001 98: 3495–3496

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr Mariano Rocchi (RMC) for providing the IGKC and IGLC probes, Prof Gilber Lenoir (IARC) for providing the cell lines; Erik Kjærsgaard, Ulla Høy Davidsen and Dr Charles Medom Hansen for reading the manuscript and Marianne Lodahl for help with sequencing. This work was supported by the Danish Cancer Society and the Danish National Research Foundation.

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Author notes

  1. TS Poulsen and AN Silahtaroglu: The first two authors have contributed to the work equally

Authors and Affiliations

  1. Department of Haematology L, The Research Laboratory, Herlev Hospital, University of Copenhagen, Denmark

    TS Poulsen, CG Gisselø & HE Johnsen

  2. Department of Medical Genetics, Wilhelm Johannsen Centre for Functional Genome Research, IMBG, Panum Institute, University of Copenhagen, Denmark

    AN Silahtaroglu & N Tommerup

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  1. TS Poulsen
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Poulsen, T., Silahtaroglu, A., Gisselø, C. et al. Detection of illegitimate rearrangements within the immunoglobulin light chain loci in B cell malignancies using end sequenced probes. Leukemia 16, 2148–2155 (2002). https://doi.org/10.1038/sj.leu.2402648

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