Virchows Archiv

, Volume 450, Issue 5, pp 559–565 | Cite as

Molecular cytogenetic characterization of t(14;19)(q32;p13), a new recurrent translocation in B cell malignancies

  • Francesca MicciEmail author
  • Ioannis Panagopoulos
  • Geir E. Tjønnfjord
  • Arne Kolstad
  • Jan Delabie
  • Klaus Beiske
  • Sverre Heim
Original Article


Translocations involving an immunoglobulin (IG) locus are a recurring theme in B cell neoplasia. The rearrangements lead to the joining of an IG gene with a (proto)oncogene, whereby the latter comes under the influence of transcription-stimulating sequences in the constitutively active IG locus resulting in deregulation of the oncogene and neoplastic growth. We present here three cases of B cell neoplasia that showed a t(14;19)(q32;p13) by karyotypic analysis. Detailed molecular cytogenetic characterization of the breakpoints on chromosomes 14 and 19 in the two cases from which extra material was available, demonstrated the involvement of the immunoglobulin heavy-chain (IGH@)-variable region on chromosome 14 in both and, in one case, that the breakpoint was within the BRD4 gene on chromosome 19. Against the background of what one knows about IGH@ involvement in lymphatic malignancies, it is difficult to envisage a fusion gene with qualitatively altered protein product as the crucial pathogenetic outcome of the translocation. In spite of the fact that we found BRD4 split by the t(14;19)(q32;p13) in one of the two informative cases, we cannot be sure that this was the pathogenetically relevant target gene. Other pathogenetic possibilities could be deregulation of the neighboring NOTCH3 and/or ABHD9 genes, located distal to BRD4 in 19p13.


ALL Large B cell lymphoma Cytogenetics t(14;19)(q32;p13) BRD4 



This work was supported by grants from the Norwegian Cancer Society, COST Action B-19—Molecular cytogenetics of solid tumors—Short-term Scientific Mission programme, the Gunnar Nilsson’s Cancer Foundation, and The Swedish Children’s Cancer Foundation.


  1. 1.
    Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol 6:635–645PubMedCrossRefGoogle Scholar
  2. 2.
    Au WY, Horsman DE, Ohno H, Klasa RJ, Gascoyne RD (2002) Bcl-3/IgH translocation (14;19)(q32;q13) in non-Hodgkin’s lymphomas. Leuk Lymphoma 43:813–816PubMedCrossRefGoogle Scholar
  3. 3.
    Axelson H (2004) Notch signaling and cancer: emerging complexity. Semin Cancer Biol 14:317–319PubMedCrossRefGoogle Scholar
  4. 4.
    Bellavia D, Campese AF, Checquolo S, Balestri A, Biondi A, Cazzaniga G, Lendahl U, Fehling HJ, Hayday AC, Frati L, von Boehmer H, Gulino A, Screpanti I (2002) Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc Natl Acad Sci USA 99:3788–3793PubMedCrossRefGoogle Scholar
  5. 5.
    Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van’t Veer MB (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9:1783–1786PubMedGoogle Scholar
  6. 6.
    Campbell LJ (2005) Cytogenetics of lymphomas. Pathology 37:493–507PubMedCrossRefGoogle Scholar
  7. 7.
    Czepulkowski B, Gibbons B (2001) Cytogenetics in acute lymphoblastic leukemia. In: Rooney DE (ed) Human cytogenetics: malignancy and acquired abnormalities. Oxford University Press, Oxford, pp 57–85Google Scholar
  8. 8.
    Dang TP, Gazdar AF, Virmani AK, Sepetavec T, Hande KR, Minna JD, Roberts JR, Carbone DP (2000) Chromosome 19 translocation, overexpression of Notch3, and human lung cancer. J Natl Cancer Inst 92:1355–1357PubMedCrossRefGoogle Scholar
  9. 9.
    Douet-Guilbert N, Morel F, Le Bris MJ, Herry A, Le Calvez G, Marion V, Abgrall JF, Berthou C, De Braekeleer M (2004) Cytogenetic studies in T-cell acute lymphoblastic leukemia (1981–2002). Leuk Lymphoma 45:287–290PubMedCrossRefGoogle Scholar
  10. 10.
    Evensen SA, Brinch L, Tjonnfjord G, Stavem P, Wisloff F (1994) Estimated 8-year survival of more than 40% in a population-based study of 79 adult patients with acute lymphoblastic leukaemia. Br J Haematol 88:88–93PubMedGoogle Scholar
  11. 11.
    Finn WG, Thangavelu M, Yelavarthi KK, Goolsby CL, Tallman MS, Traynor A, Peterson LC (1996) Karyotype correlates with peripheral blood morphology and immunophenotype in chronic lymphocytic leukemia. Am J Clin Pathol 105:458–467PubMedGoogle Scholar
  12. 12.
    French CA, Kutok JL, Faquin WC, Toretsky JA, Antonescu CR, Griffin CA, Nose V, Vargas SO, Moschovi M, Tzortzatou-Stathopoulou F, Miyoshi I, Perez-Atayde AR, Aster JC, Fletcher JA (2004) Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22:4135–4139PubMedCrossRefGoogle Scholar
  13. 13.
    French CA, Miyoshi I, Aster JC, Kubonishi I, Kroll TG, Dal Cin P, Vargas SO, Perez-Atayde AR, Fletcher JA (2001) BRD4 bromodomain gene rearrangement in aggressive carcinoma with translocation t(15;19). Am J Pathol 159:1987–1992PubMedGoogle Scholar
  14. 14.
    French CA, Miyoshi I, Kubonishi I, Grier HE, Perez-Atayde AR, Fletcher JA (2003) BRD4–NUT fusion oncogene: a novel mechanism in aggressive carcinoma. Cancer Res 63:304–307PubMedGoogle Scholar
  15. 15.
    Haruki N, Kawaguchi KS, Eichenberger S, Massion PP, Gonzalez A, Gazdar AF, Minna JD, Carbone DP, Dang TP (2005) Cloned fusion product from a rare t(15;19)(q13.2;p13.1) inhibit S phase in vitro. J Med Genet 42:558–564PubMedCrossRefGoogle Scholar
  16. 16.
    Heim S, Mitelman F (eds) (1995) Cancer cytogenetics. Wiley-Liss, New YorkGoogle Scholar
  17. 17.
    Shaffer LG, Tommerup N (eds) (2005) ISCN 2005: an international system for human cytogenetic nomenclature. S Karger, BaselGoogle Scholar
  18. 18.
    Kearny L, Hammomd DW (2001) Molecular cytogenetic technologies. In: Rooney DE (ed) Human cytogenetics—malignancy and acquired abnormalities. Oxford University Press, Oxford, pp 129–163Google Scholar
  19. 19.
    Martinez-Climent JA, Sanchez-Izquierdo D, Sarsotti E, Blesa D, Benet I, Climent J, Vizcarra E, Marugan I, Terol MJ, Sole F, Cigudosad JC, Siebert R, Dyer MJ, Garcia-Conde J (2003) Genomic abnormalities acquired in the blastic transformation of splenic marginal zone B-cell lymphoma. Leuk Lymphoma 44:459–464PubMedCrossRefGoogle Scholar
  20. 20.
    Maruyama T, Farina A, Dey A, Cheong J, Bermudez VP, Tamura T, Sciortino S, Shuman J, Hurwitz J, Ozato K (2002) A Mammalian bromodomain protein, brd4, interacts with replication factor C and inhibits progression to S phase. Mol Cell Biol 22:6509–6520PubMedCrossRefGoogle Scholar
  21. 21.
    McKeithan TW, Takimoto GS, Ohno H, Bjorling VS, Morgan R, Hecht BK, Dube I, Sandberg AA, Rowley JD (1997) BCL3 rearrangements and t(14;19) in chronic lymphocytic leukemia and other B-cell malignancies: a molecular and cytogenetic study. Genes Chromosomes Cancer 20:64–72PubMedCrossRefGoogle Scholar
  22. 22.
    Mitelman, F., Johansson, B., Mertens, F. (2006) Mitelman database of chromosome aberrations in cancer.
  23. 23.
    Ohno H, Doi S, Yabumoto K, Fukuhara S, McKeithan TW (1993) Molecular characterization of the t(14;19)(q32;q13) translocation in chronic lymphocytic leukemia. Leukemia 7:2057–2063PubMedGoogle Scholar
  24. 24.
    Popescu NC, Zimonjic DB (2002) Chromosome-mediated alterations of the MYC gene in human cancer. J Cell Mol Med 6:151–159PubMedCrossRefGoogle Scholar
  25. 25.
    Robinson HM, Taylor KE, Jalali GR, Cheung KL, Harrison CJ, Moorman AV (2004) t(14;19)(q32;q13): a recurrent translocation in B-cell precursor acute lymphoblastic leukemia. Genes Chromosomes Cancer 39:88–92PubMedCrossRefGoogle Scholar
  26. 26.
    Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  27. 27.
    Schlegelberger B, Weber-Matthiesen K, Himmler A, Bartels H, Sonnen R, Kuse R, Feller AC, Grote W (1994) Cytogenetic findings and results of combined immunophenotyping and karyotyping in Hodgkin’s disease. Leukemia 8:72–80PubMedGoogle Scholar
  28. 28.
    Sonoki T, Willis TG, Oscier DG, Karran EL, Siebert R, Dyer MJ (2004) Rapid amplification of immunoglobulin heavy chain switch (IGHS) translocation breakpoints using long-distance inverse PCR. Leukemia 18:2026–2031PubMedCrossRefGoogle Scholar
  29. 29.
    Willis TG, Jadayel DM, Coignet LJ, Abdul-Rauf M, Treleaven JG, Catovsky D, Dyer MJ (1997) Rapid molecular cloning of rearrangements of the IGHJ locus using long-distance inverse polymerase chain reaction. Blood 90:2456–2464PubMedGoogle Scholar
  30. 30.
    Zagouras P, Stifani S, Blaumueller CM, Carcangiu ML, Artavanis-Tsakonas S (1995) Alterations in Notch signaling in neoplastic lesions of the human cervix. Proc Natl Acad Sci USA 92:6414–6418PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Francesca Micci
    • 1
    Email author
  • Ioannis Panagopoulos
    • 2
  • Geir E. Tjønnfjord
    • 3
    • 6
  • Arne Kolstad
    • 4
  • Jan Delabie
    • 5
  • Klaus Beiske
    • 5
  • Sverre Heim
    • 1
    • 6
  1. 1.Department of Medical GeneticsRikshospitalet-Radiumhospitalet Medical Centre (Montebello)OsloNorway
  2. 2.Department of Clinical GeneticsUniversity HospitalLundSweden
  3. 3.Medical Department, Division of HematologyRikshospitalet-Radiumhospitalet Medical Centre (Gaustad)OsloNorway
  4. 4.Department of OncologyRikshospitalet-Radiumhospitalet Medical Centre (Montebello)OsloNorway
  5. 5.Department of PathologyRikshospitalet-Radiumhospitalet Medical Centre (Montebello)OsloNorway
  6. 6.Faculty of MedicineUniversity of OsloOsloNorway

Personalised recommendations