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. 1984 Dec 1;3(12):2951–2955. doi: 10.1002/j.1460-2075.1984.tb02239.x

c-myc and immunoglobulin kappa light chain constant genes are on the 8q+ chromosome of three Burkitt lymphoma lines with t(2;8) translocations.

G A Rappold, H Hameister, T Cremer, S Adolph, B Henglein, U K Freese, G M Lenoire, G W Bornkamm
PMCID: PMC557796  PMID: 6441706

Abstract

We have determined the localization of c-myc and the immunoglobulin kappa light chain genes on the 8q+/2p- chromosomes of the three Burkitt lymphoma lines BL21, LY66 and LY91 with t(2;8) translocation by in situ hybridization. BL21 is characterized by a complex translocation in which a piece of chromosome 9 appears to be located between the fragments of chromosome 8 and 2 on the 8q+ chromosome. Our data indicate that in all three cell lines the c-myc gene is located on the 8q+ chromosome proximal to the breakpoint in band 8q24. In all cell lines examined the cluster of kappa variable genes has remained on the 2p- chromosome. In LY91 cells the major part of the joining region remained on 2p-, while the joining region has moved to 8q+ in the cell lines BL21 and LY66. In all three cell lines the constant kappa light chain gene was found on the 8q+ chromosome. The fact that an essentially identical pattern was found in the cell line BL21, with the complex translocation, suggests that the insertion of the piece of chromosome 9 into the 8q+ chromosome might be a secondary event. Our present data fit into the concept that in all Burkitt lymphoma lines investigated so far, including cases with t(8;14) and the variant translocations t(2;8) and t(8;22), the c-myc gene becomes situated at the 5' side of an immunoglobulin constant gene. This may have implications for the generation of somatic mutations in the coding and non-coding part of the c-myc gene.

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Selected References

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

  1. Adams J. M., Gerondakis S., Webb E., Corcoran L. M., Cory S. Cellular myc oncogene is altered by chromosome translocation to an immunoglobulin locus in murine plasmacytomas and is rearranged similarly in human Burkitt lymphomas. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1982–1986. doi: 10.1073/pnas.80.7.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., Lenoir G., Leder P. The human c-myc oncogene: structural consequences of translocation into the IgH locus in Burkitt lymphoma. Cell. 1983 Oct;34(3):779–787. doi: 10.1016/0092-8674(83)90534-2. [DOI] [PubMed] [Google Scholar]
  3. Bentley D. L., Rabbitts T. H. Human V kappa immunoglobulin gene number: implications for the origin of antibody diversity. Cell. 1981 Jun;24(3):613–623. doi: 10.1016/0092-8674(81)90088-x. [DOI] [PubMed] [Google Scholar]
  4. Bernard O., Cory S., Gerondakis S., Webb E., Adams J. M. Sequence of the murine and human cellular myc oncogenes and two modes of myc transcription resulting from chromosome translocation in B lymphoid tumours. EMBO J. 1983;2(12):2375–2383. doi: 10.1002/j.1460-2075.1983.tb01749.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bernheim A., Berger R., Lenoir G. Cytogenetic studies on African Burkitt's lymphoma cell lines: t(8;14), t(2;8) and t(8;22) translocations. Cancer Genet Cytogenet. 1981 Jun;3(4):307–315. doi: 10.1016/0165-4608(81)90039-x. [DOI] [PubMed] [Google Scholar]
  6. Bornkamm G. W., Hudewentz J., Freese U. K., Zimber U. Deletion of the nontransforming Epstein-Barr virus strain P3HR-1 causes fusion of the large internal repeat to the DSL region. J Virol. 1982 Sep;43(3):952–968. doi: 10.1128/jvi.43.3.952-968.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bornkamm G. W., Kaduk B., Kachel G., Schneider U., Fresen K. O., Schwanitz G., Hermanek P. Epstein-Barr virus-positive Burkitt's lymphoma in a German woman during pregnancy. Blut. 1980 Mar;40(3):167–177. doi: 10.1007/BF01008574. [DOI] [PubMed] [Google Scholar]
  8. Clewell D. B., Helinski D. R. Supercoiled circular DNA-protein complex in Escherichia coli: purification and induced conversion to an opern circular DNA form. Proc Natl Acad Sci U S A. 1969 Apr;62(4):1159–1166. doi: 10.1073/pnas.62.4.1159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Croce C. M., Shander M., Martinis J., Cicurel L., D'Ancona G. G., Dolby T. W., Koprowski H. Chromosomal location of the genes for human immunoglobulin heavy chains. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3416–3419. doi: 10.1073/pnas.76.7.3416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Croce C. M., Thierfelder W., Erikson J., Nishikura K., Finan J., Lenoir G. M., Nowell P. C. Transcriptional activation of an unrearranged and untranslocated c-myc oncogene by translocation of a C lambda locus in Burkitt. Proc Natl Acad Sci U S A. 1983 Nov;80(22):6922–6926. doi: 10.1073/pnas.80.22.6922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Dalla-Favera R., Martinotti S., Gallo R. C., Erikson J., Croce C. M. Translocation and rearrangements of the c-myc oncogene locus in human undifferentiated B-cell lymphomas. Science. 1983 Feb 25;219(4587):963–967. doi: 10.1126/science.6401867. [DOI] [PubMed] [Google Scholar]
  13. Davis M., Malcolm S., Rabbitts T. H. Chromosome translocation can occur on either side of the c-myc oncogene in Burkitt lymphoma cells. Nature. 1984 Mar 15;308(5956):286–288. doi: 10.1038/308286a0. [DOI] [PubMed] [Google Scholar]
  14. Emanuel B. S., Selden J. R., Chaganti R. S., Jhanwar S., Nowell P. C., Croce C. M. The 2p breakpoint of a 2;8 translocation in Burkitt lymphoma interrupts the V kappa locus. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2444–2446. doi: 10.1073/pnas.81.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Erikson J., Martinis J., Croce C. M. Assignment of the genes for human lambda immunoglobulin chains to chromosome 22. Nature. 1981 Nov 12;294(5837):173–175. doi: 10.1038/294173a0. [DOI] [PubMed] [Google Scholar]
  16. Erikson J., Nishikura K., ar-Rushdi A., Finan J., Emanuel B., Lenoir G., Nowell P. C., Croce C. M. Translocation of an immunoglobulin kappa locus to a region 3' of an unrearranged c-myc oncogene enhances c-myc transcription. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7581–7585. doi: 10.1073/pnas.80.24.7581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gerhard D. S., Kawasaki E. S., Bancroft F. C., Szabo P. Localization of a unique gene by direct hybridization in situ. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3755–3759. doi: 10.1073/pnas.78.6.3755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hamlyn P. H., Rabbitts T. H. Translocation joins c-myc and immunoglobulin gamma 1 genes in a Burkitt lymphoma revealing a third exon in the c-myc oncogene. Nature. 1983 Jul 14;304(5922):135–139. doi: 10.1038/304135a0. [DOI] [PubMed] [Google Scholar]
  19. Hieter P. A., Max E. E., Seidman J. G., Maizel J. V., Jr, Leder P. Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments. Cell. 1980 Nov;22(1 Pt 1):197–207. doi: 10.1016/0092-8674(80)90168-3. [DOI] [PubMed] [Google Scholar]
  20. Hobart M. J., Rabbitts T. H., Goodfellow P. N., Solomon E., Chambers S., Spurr N., Povey S. Immunoglobulin heavy chain genes in humans are located on chromosome. Ann Hum Genet. 1981 Oct;45(Pt 4):331–335. doi: 10.1111/j.1469-1809.1981.tb00346.x. [DOI] [PubMed] [Google Scholar]
  21. Hollis G. F., Mitchell K. F., Battey J., Potter H., Taub R., Lenoir G. M., Leder P. A variant translocation places the lambda immunoglobulin genes 3' to the c-myc oncogene in Burkitt's lymphoma. Nature. 1984 Feb 23;307(5953):752–755. doi: 10.1038/307752a0. [DOI] [PubMed] [Google Scholar]
  22. Kirsch I. R., Morton C. C., Nakahara K., Leder P. Human immunoglobulin heavy chain genes map to a region of translocations in malignant B lymphocytes. Science. 1982 Apr 16;216(4543):301–303. doi: 10.1126/science.6801764. [DOI] [PubMed] [Google Scholar]
  23. Klein G. Specific chromosomal translocations and the genesis of B-cell-derived tumors in mice and men. Cell. 1983 Feb;32(2):311–315. doi: 10.1016/0092-8674(83)90449-x. [DOI] [PubMed] [Google Scholar]
  24. Malcolm S., Barton P., Murphy C., Ferguson-Smith M. A., Bentley D. L., Rabbitts T. H. Localization of human immunoglobulin kappa light chain variable region genes to the short arm of chromosome 2 by in situ hybridization. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4957–4961. doi: 10.1073/pnas.79.16.4957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Manolov G., Manolova Y. Marker band in one chromosome 14 from Burkitt lymphomas. Nature. 1972 May 5;237(5349):33–34. doi: 10.1038/237033a0. [DOI] [PubMed] [Google Scholar]
  26. Manolova Y., Manolov G., Kieler J., Levan A., Klein G. Genesis of the 14q+ marker in Burkitt's lymphoma. Hereditas. 1979;90(1):5–10. doi: 10.1111/j.1601-5223.1979.tb01288.x. [DOI] [PubMed] [Google Scholar]
  27. McBride O. W., Hieter P. A., Hollis G. F., Swan D., Otey M. C., Leder P. Chromosomal location of human kappa and lambda immunoglobulin light chain constant region genes. J Exp Med. 1982 May 1;155(5):1480–1490. doi: 10.1084/jem.155.5.1480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Neel B. G., Jhanwar S. C., Chaganti R. S., Hayward W. S. Two human c-onc genes are located on the long arm of chromosome 8. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7842–7846. doi: 10.1073/pnas.79.24.7842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Philip T., Lenoir G. M., Fraisse J., Philip I., Bertoglio J., Ladjaj S., Bertrand S., Brunat-Mentigny M. EBV-positive Burkitt's lymphoma from Algeria, with a three-way rearrangement involving chromosomes 2, 8 and 9. Int J Cancer. 1981 Oct 15;28(4):417–420. doi: 10.1002/ijc.2910280404. [DOI] [PubMed] [Google Scholar]
  30. Polack A., Delius H., Zimber U., Bornkamm G. W. Two deletions in the Epstein-Barr virus genome of the Burkitt lymphoma nonproducer line Raji. Virology. 1984 Feb;133(1):146–157. doi: 10.1016/0042-6822(84)90433-1. [DOI] [PubMed] [Google Scholar]
  31. Rabbitts T. H., Forster A., Hamlyn P., Baer R. Effect of somatic mutation within translocated c-myc genes in Burkitt's lymphoma. Nature. 1984 Jun 14;309(5969):592–597. doi: 10.1038/309592a0. [DOI] [PubMed] [Google Scholar]
  32. Rabbitts T. H., Hamlyn P. H., Baer R. Altered nucleotide sequences of a translocated c-myc gene in Burkitt lymphoma. Nature. 1983 Dec 22;306(5945):760–765. doi: 10.1038/306760a0. [DOI] [PubMed] [Google Scholar]
  33. Rappold G. A., Cremer T., Cremer C., Back W., Bogenberger J., Cooke H. J. Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes. Hum Genet. 1984;65(3):257–261. doi: 10.1007/BF00286513. [DOI] [PubMed] [Google Scholar]
  34. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  35. Rowley J. D. Identification of the constant chromosome regions involved in human hematologic malignant disease. Science. 1982 May 14;216(4547):749–751. doi: 10.1126/science.7079737. [DOI] [PubMed] [Google Scholar]
  36. Saito H., Hayday A. C., Wiman K., Hayward W. S., Tonegawa S. Activation of the c-myc gene by translocation: a model for translational control. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7476–7480. doi: 10.1073/pnas.80.24.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Taub R., Kelly K., Battey J., Latt S., Lenoir G. M., Tantravahi U., Tu Z., Leder P. A novel alteration in the structure of an activated c-myc gene in a variant t(2;8) Burkitt lymphoma. Cell. 1984 Jun;37(2):511–520. doi: 10.1016/0092-8674(84)90381-7. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Taub R., Moulding C., Battey J., Murphy W., Vasicek T., Lenoir G. M., Leder P. Activation and somatic mutation of the translocated c-myc gene in burkitt lymphoma cells. Cell. 1984 Feb;36(2):339–348. doi: 10.1016/0092-8674(84)90227-7. [DOI] [PubMed] [Google Scholar]
  41. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  42. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Watt R., Nishikura K., Sorrentino J., ar-Rushdi A., Croce C. M., Rovera G. The structure and nucleotide sequence of the 5' end of the human c-myc oncogene. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6307–6311. doi: 10.1073/pnas.80.20.6307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zech L., Haglund U., Nilsson K., Klein G. Characteristic chromosomal abnormalities in biopsies and lymphoid-cell lines from patients with Burkitt and non-Burkitt lymphomas. Int J Cancer. 1976 Jan 15;17(1):47–56. doi: 10.1002/ijc.2910170108. [DOI] [PubMed] [Google Scholar]
  45. ar-Rushdi A., Nishikura K., Erikson J., Watt R., Rovera G., Croce C. M. Differential expression of the translocated and the untranslocated c-myc oncogene in Burkitt lymphoma. Science. 1983 Oct 28;222(4622):390–393. doi: 10.1126/science.6414084. [DOI] [PubMed] [Google Scholar]
  46. de la Chapelle A., Lenoir G., Boué J., Boué A., Gallano P., Huerre C., Szajnert M. F., Jeanpierre M., Lalouel J. M., Kaplan J. C. Lambda Ig constant region genes are translocated to chromosome 8 in Burkitt's lymphoma with t(8;22). Nucleic Acids Res. 1983 Feb 25;11(4):1133–1142. doi: 10.1093/nar/11.4.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]

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