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. 1992 Nov;66(5):805–809. doi: 10.1038/bjc.1992.364

The detection of specific gene rearrangements in non-Hodgkin's lymphoma using the polymerase chain reaction.

N Corbally 1, L Grogan 1, P A Dervan 1, D N Carney 1
PMCID: PMC1978002  PMID: 1419624

Abstract

Characteristic gene rearrangements are present in most non-Hodgkin's lymphomas (NHL). These are usually detected by Southern blotting techniques. In this study, the ability of the polymerase chain reaction (PCR) to detect the t(14;18) chromosomal translocation and immunoglobulin heavy chain (IgH) gene rearrangement was evaluated. DNA from 14 follicular and 42 diffuse B-cell lymphomas was examined using oligonucleotide primers specific for opposing sides of the IgH gene rearrangement on chromosome 14 (towards conserved VH and JH sequences) and opposing sides of the t(14;18) chromosomal translocation (towards the major breakpoint region of the bcl-2 gene on chromosome 18 and conserved JH sequence on chromosome 14). The t(14;18) translocation was detected in 57% of follicular lymphomas and 21% of diffuse B-cell lymphomas. Clonal IgH gene rearrangements using PCR were detected in 50% follicular and 52% of the diffuse lymphomas. Either or both of these rearrangements were detected in 93% follicular and in 59% of diffuse lymphomas. PCR is a rapid and easy technique that can detect the abnormal rearrangement of the bcl-2 gene and clonal IgH rearrangement, indicating the presence of lymphoma. This may be of benefit in monitoring response to therapy and in predicting prognosis in this disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bakhshi A., Jensen J. P., Goldman P., Wright J. J., McBride O. W., Epstein A. L., Korsmeyer S. J. Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around JH on chromosome 14 and near a transcriptional unit on 18. Cell. 1985 Jul;41(3):899–906. doi: 10.1016/s0092-8674(85)80070-2. [DOI] [PubMed] [Google Scholar]
  2. Cleary M. L., Galili N., Sklar J. Detection of a second t(14;18) breakpoint cluster region in human follicular lymphomas. J Exp Med. 1986 Jul 1;164(1):315–320. doi: 10.1084/jem.164.1.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cleary M. L., Sklar J. Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7439–7443. doi: 10.1073/pnas.82.21.7439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cleary M. L., Smith S. D., Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. Cell. 1986 Oct 10;47(1):19–28. doi: 10.1016/0092-8674(86)90362-4. [DOI] [PubMed] [Google Scholar]
  5. Cotter F. E., Price C., Meerabux J., Zucca E., Young B. D. Direct sequence analysis of 14q+ and 18q- chromosome junctions at the MBR and MCR revealing clustering within the MBR in follicular lymphoma. Ann Oncol. 1991 Feb;2 (Suppl 2):93–97. doi: 10.1007/978-1-4899-7305-4_15. [DOI] [PubMed] [Google Scholar]
  6. Crescenzi M., Seto M., Herzig G. P., Weiss P. D., Griffith R. C., Korsmeyer S. J. Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4869–4873. doi: 10.1073/pnas.85.13.4869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Croce C. M., Nowell P. C. Molecular basis of human B cell neoplasia. Blood. 1985 Jan;65(1):1–7. [PubMed] [Google Scholar]
  8. Dalla-Favera R., Bregni M., Erikson J., Patterson D., Gallo R. C., Croce C. M. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824–7827. doi: 10.1073/pnas.79.24.7824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Desiderio S. V., Yancopoulos G. D., Paskind M., Thomas E., Boss M. A., Landau N., Alt F. W., Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984 Oct 25;311(5988):752–755. doi: 10.1038/311752a0. [DOI] [PubMed] [Google Scholar]
  10. Eick S., Krieger G., Bolz I., Kneba M. Sequence analysis of amplified t(14;18) chromosomal breakpoints in B-cell lymphomas. J Pathol. 1990 Oct;162(2):127–133. doi: 10.1002/path.1711620205. [DOI] [PubMed] [Google Scholar]
  11. Fisher R. I., Longo D. L., DeVita V. T., Jr, Hubbard S. M., Miller T. P., Young R. C. Long-term follow-up of ProMACE-CytaBOM in non-Hodgkin's lymphomas. Ann Oncol. 1991 Jan;2 (Suppl 1):33–35. doi: 10.1093/annonc/2.suppl_1.33. [DOI] [PubMed] [Google Scholar]
  12. Flanagan J. G., Rabbitts T. H. The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes. EMBO J. 1982;1(5):655–660. doi: 10.1002/j.1460-2075.1982.tb01223.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gribben J. G., Freedman A. S., Neuberg D., Roy D. C., Blake K. W., Woo S. D., Grossbard M. L., Rabinowe S. N., Coral F., Freeman G. J. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med. 1991 Nov 28;325(22):1525–1533. doi: 10.1056/NEJM199111283252201. [DOI] [PubMed] [Google Scholar]
  14. Jagannath S., Velasquez W. S., Tucker S. L., Manning J. T., McLaughlin P., Fuller L. M. Stage IV diffuse large-cell lymphoma: a long-term analysis. J Clin Oncol. 1985 Jan;3(1):39–47. doi: 10.1200/JCO.1985.3.1.39. [DOI] [PubMed] [Google Scholar]
  15. Kwok S., Higuchi R. Avoiding false positives with PCR. Nature. 1989 May 18;339(6221):237–238. doi: 10.1038/339237a0. [DOI] [PubMed] [Google Scholar]
  16. Lee M. S., Chang K. S., Cabanillas F., Freireich E. J., Trujillo J. M., Stass S. A. Detection of minimal residual cells carrying the t(14;18) by DNA sequence amplification. Science. 1987 Jul 10;237(4811):175–178. doi: 10.1126/science.3110950. [DOI] [PubMed] [Google Scholar]
  17. Lipford E., Wright J. J., Urba W., Whang-Peng J., Kirsch I. R., Raffeld M., Cossman J., Longo D. L., Bakhshi A., Korsmeyer S. J. Refinement of lymphoma cytogenetics by the chromosome 18q21 major breakpoint region. Blood. 1987 Dec;70(6):1816–1823. [PubMed] [Google Scholar]
  18. McCarthy K. P., Sloane J. P., Wiedemann L. M. Rapid method for distinguishing clonal from polyclonal B cell populations in surgical biopsy specimens. J Clin Pathol. 1990 May;43(5):429–432. doi: 10.1136/jcp.43.5.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989 Apr 7;57(1):79–88. doi: 10.1016/0092-8674(89)90174-8. [DOI] [PubMed] [Google Scholar]
  20. Ngan B. Y., Nourse J., Cleary M. L. 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 May 15;73(7):1759–1762. [PubMed] [Google Scholar]
  21. Nguyen T. D. Southern blot analysis of polymerase chain reaction products on acrylamide gels. Biotechniques. 1989 Mar;7(3):238–240. [PubMed] [Google Scholar]
  22. Picker L. J., Weiss L. M., Medeiros L. J., Wood G. S., Warnke R. A. Immunophenotypic criteria for the diagnosis of non-Hodgkin's lymphoma. Am J Pathol. 1987 Jul;128(1):181–201. [PMC free article] [PubMed] [Google Scholar]
  23. Rowley J. D., Fukuhara S. Chromosome studies in non-Hodgkin's lymphomas. Semin Oncol. 1980 Sep;7(3):255–266. [PubMed] [Google Scholar]
  24. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  25. Shibata D., Hu E., Weiss L. M., Brynes R. K., Nathwani B. N. Detection of specific t(14;18) chromosomal translocations in fixed tissues. Hum Pathol. 1990 Feb;21(2):199–203. doi: 10.1016/0046-8177(90)90129-s. [DOI] [PubMed] [Google Scholar]
  26. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  27. Taub R., Kirsch I., Morton C., Lenoir G., Swan D., Tronick S., Aaronson S., Leder P. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt lymphoma and murine plasmacytoma cells. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837–7841. doi: 10.1073/pnas.79.24.7837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  29. Tsujimoto Y., Cossman J., Jaffe E., Croce C. M. Involvement of the bcl-2 gene in human follicular lymphoma. Science. 1985 Jun 21;228(4706):1440–1443. doi: 10.1126/science.3874430. [DOI] [PubMed] [Google Scholar]
  30. Tsujimoto Y., Gorham J., Cossman J., Jaffe E., Croce C. M. The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. Science. 1985 Sep 27;229(4720):1390–1393. doi: 10.1126/science.3929382. [DOI] [PubMed] [Google Scholar]
  31. Waldmann T. A. The arrangement of immunoglobulin and T cell receptor genes in human lymphoproliferative disorders. Adv Immunol. 1987;40:247–321. doi: 10.1016/s0065-2776(08)60241-2. [DOI] [PubMed] [Google Scholar]
  32. Wan J. H., Trainor K. J., Brisco M. J., Morley A. A. Monoclonality in B cell lymphoma detected in paraffin wax embedded sections using the polymerase chain reaction. J Clin Pathol. 1990 Nov;43(11):888–890. doi: 10.1136/jcp.43.11.888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Weiss L. M., Warnke R. A., Sklar J., Cleary M. L. Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphomas. N Engl J Med. 1987 Nov 5;317(19):1185–1189. doi: 10.1056/NEJM198711053171904. [DOI] [PubMed] [Google Scholar]
  34. Yunis J. J., Frizzera G., Oken M. M., McKenna J., Theologides A., Arnesen M. Multiple recurrent genomic defects in follicular lymphoma. A possible model for cancer. N Engl J Med. 1987 Jan 8;316(2):79–84. doi: 10.1056/NEJM198701083160204. [DOI] [PubMed] [Google Scholar]
  35. Yunis J. J., Mayer M. G., Arnesen M. A., Aeppli D. P., Oken M. M., Frizzera G. bcl-2 and other genomic alterations in the prognosis of large-cell lymphoma. N Engl J Med. 1989 Apr 20;320(16):1047–1054. doi: 10.1056/NEJM198904203201605. [DOI] [PubMed] [Google Scholar]
  36. Yunis J. J. New chromosome techniques in the study of human neoplasia. Hum Pathol. 1981 Jun;12(6):540–549. doi: 10.1016/s0046-8177(81)80068-8. [DOI] [PubMed] [Google Scholar]
  37. Yunis J. J., Oken M. M., Kaplan M. E., Ensrud K. M., Howe R. R., Theologides A. Distinctive chromosomal abnormalities in histologic subtypes of non-Hodgkin's lymphoma. N Engl J Med. 1982 Nov 11;307(20):1231–1236. doi: 10.1056/NEJM198211113072002. [DOI] [PubMed] [Google Scholar]

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