High Frequency ofBCL2 Translocation in Thai Patients with Follicular Lymphomas


Follicular lymphoma is characterized by chromosomal translocation involvingBCL2 and immunoglobulin heavy chain genes (IgH). That the incidence of follicular lymphoma and the previously reported frequency ofBCL2 translocation are lower in Asians than in Caucasians implies a different molecular pathology. The study ofBCL2 rearrangement will yield deeper insights into the pathogenesis of follicular lymphomas and into clinical applications of molecular diagnosis for Asian follicular lymphoma patients.BCL2 /IgH translocation was analyzed in paraffin-embedded tissues from follicular lymphoma patients by using polymerase chain reaction (PCR) analysis of the major breakpoint region (MBR), the intermediate cluster region (ICR), and the minor cluster region. In addition, fluorescence in situ hybridization (FISH) analysis with split-signalBCL2 probes was performed. PCR analysis revealedBCL2 rearrangement in 12 (23.5%) of 51 cases (10 MBR and 2 ICR breakpoints).This frequency is lower than the frequencies reported from Western countries (40%–60%). DNA sequencing of the breakpoints revealed nucleotide insertions suggesting V(D)J recombination-mediated mechanisms. On the other hand, FISH analysis revealed 11 (84.6%) of 13 cases with positive signals forBCL2 translocation. Our results suggest thatBCL2 translocation is essential for the pathogenesis of follicular lymphoma in Thai patients. In addition, the data demonstrate the low sensitivity of the PCR for diagnostic testing and suggest that split-signal FISH is the method of choice.

This is a preview of subscription content, log in to check access.


  1. 1.

    Limpens J, de Jong D, van Krieken JH, et al. Bcl-2/JH rearrangements in benign lymphoid tissues with follicular hyperplasia.Oncogene. 1991;6:2271–2276.

    PubMed  PubMed Central  CAS  Google Scholar 

  2. 2.

    de Jong D. Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors.J Clin Oncol. 2005;23:6358–6363.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Biagi JJ, Seymour JF. Insights into the molecular pathogenesis of follicular lymphoma arising from analysis of geographic variation.Blood. 2002;99:4265–4275.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. 4.

    Intragumtornchai T, Wannakrairoj P, Chaimongkol B, et al. Non-Hodgkin’s lymphomas in Thailand: a retrospective pathologic and clinical analysis of 1391 cases.Cancer. 1996;78:1813–1819.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. 5.

    Sukpanichnant S, Sonakul D, Piankijagum A, et al. Malignant lymphoma in Thailand: changes in the frequency of malignant lymphoma determined from a histopathologic and immunophenotypic analysis of 425 cases at Siriraj Hospital.Cancer. 1998;83:1197–1204.

    Article  CAS  Google Scholar 

  6. 6.

    Yasukawa M, Bando S, Dölken G, et al. Low frequency ofBCL-2/J H translocation in peripheral blood lymphocytes of healthy Japanese individuals.Blood. 2001;98:486–488.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. 7.

    Segel MJ, Paltiel O, Zimran A, et al. Geographic variance in the frequency of the t(14;18) translocation in follicular lymphoma: an Israeli series compared to the world.Blood Cells Mol Dis. 1998;24:62–72.

    Article  PubMed  CAS  Google Scholar 

  8. 8.

    Albinger-Hegyi A, Hochreutener B, Abdou MT, et al. High frequency of t(14;18)-translocation breakpoints outside of major breakpoint and minor cluster regions in follicular lymphomas: improved polymerase chain reaction protocols for their detection.Am J Pathol. 2002;160:823–832.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. 9.

    Vaandrager JW, Schuuring E, Raap T, Philippo K, Kleiverda K, Kluin P. Interphase FISH detection ofBCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes.Genes Chromosomes Cancer. 2000;27:85–94.

    Article  PubMed  CAS  Google Scholar 

  10. 10.

    Solal-Céligny P, Roy P, Colombat P, et al. Follicular Lymphoma International Prognostic Index.Blood. 2004;104:1258–1265.

    Article  PubMed  CAS  Google Scholar 

  11. 11.

    Liu J, Johnson RM, Traweek ST. Rearrangement of the BCL-2 gene in follicular lymphoma: detection by PCR in both fresh and fixed tissue samples.Diagn Mol Pathol. 1993;2:241–247.

    Article  PubMed  CAS  Google Scholar 

  12. 12.

    Greer CE, Peterson SL, Kiviat NB, Manos MM. PCR amplification from paraffin-embedded tissues: effects of fixative and fixation time.Am J Clin Pathol. 1991;95:117–124.

    Article  PubMed  CAS  Google Scholar 

  13. 13.

    Ngan BY, Nourse J, Cleary ML. Detection of chromosomal translocation t(14;18) within the minor cluster region of bcl-2 by polymerase chain reaction and direct genomic sequencing of the enzymatically amplified DNA in follicular lymphomas.Blood. 1989;73:1759–1762.

    PubMed  CAS  Google Scholar 

  14. 14.

    Gribben JG, Freedman A, Woo SD, et al. All advanced stage non-Hodgkin’s lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment.Blood. 1991;78:3275–3280.

    PubMed  CAS  Google Scholar 

  15. 15.

    Mitani S, Aoki N, Mizutani S, et al. bcl-2 gene rearrangement analysis of Japanese follicular lymphomas by polymerase chain reaction in formalin-fixed, paraffin-embedded tissue specimens.Jpn J Cancer Res. 1993;84:37–41.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. 16.

    Shaminie J, Peh SC,Tan MJ. Improvement in the detection rate of t(14;18) translocation on paraffin-embedded tissue: a combination approach using PCR and FISH.Pathology. 2003;35:414–421.

    Article  PubMed  CAS  Google Scholar 

  17. 17.

    Au WY, Fung A, Liang R. Molecular epidemiology of follicular lymphoma in Chinese: relationship with bcl-2/IgH translocation and bcl-6 397G/C polymorphism.Ann Hematol. 2005;84:506–509.

    Article  PubMed  CAS  Google Scholar 

  18. 18.

    Oehadian A, Koide N, Fianza PI, et al. Gene rearrangements in follicular lymphoma among Indonesian.Acta Med Indones. 2006;38:72–76.

    PubMed  Google Scholar 

  19. 19.

    Hirose Y, Masaki Y, Ozaki M. Fluorescence in situ hybridization detection of chromosome IGH/BCL2 translocations from paraffin-embedded tissue: evaluation in follicular lymphoma.Int J Hematol. 2003;78:154–159.

    Article  PubMed  CAS  Google Scholar 

  20. 20.

    Matsumoto Y, Nomura K, Matsumoto S, et al. Detection of t(14;18) in follicular lymphoma by dual-color fluorescence in situ hybridization on paraffin-embedded tissue sections.Cancer Genet Cytogenet. 2004;150:22–26.

    Article  PubMed  CAS  Google Scholar 

  21. 21.

    Einerson RR, Kurtin PJ, Dayharsh GA, Kimlinger TK, Remstein ED. FISH is superior to PCR in detecting t(14;18)(q32;q21)-IgH/bcl-2 in follicular lymphoma using paraffin-embedded tissue samples.Am J Clin Pathol. 2005;124:421–429.

    Article  PubMed  CAS  Google Scholar 

  22. 22.

    Peh SC, Shaminie J, Tai YC, Tan J, Gan SS. The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma.Histopathology. 2004;45:501–510.

    Article  PubMed  CAS  Google Scholar 

  23. 23.

    Jäger U, Böcskör S, Le T, et al. Follicular lymphomas’ BCL-2/IgH junctions contain templated nucleotide insertions: novel insights into the mechanism of t(14;18) translocation.Blood. 2000;95:3520–3529.

    PubMed  Google Scholar 

Download references

Author information



Corresponding authors

Correspondence to Ponlapat Rojnuckarin or Thamatorn Assanasen or Atcharaporn Chotipuech or Preecha Ruangvejvorachai or Montakarn Tansatit or Pongsak Wannakrairot or Tanin Intragumtornchai.

About this article

Cite this article

Rojnuckarin, P., Assanasen, T., Chotipuech, A. et al. High Frequency ofBCL2 Translocation in Thai Patients with Follicular Lymphomas. Int J Hematol 86, 352–357 (2007). https://doi.org/10.1532/IJH97.A20709

Download citation

Key words

  • BCL2
  • Follicular lymphoma
  • Translocation
  • Thailand
  • PCR
  • FISH