Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 May;86(9):3257–3260. doi: 10.1073/pnas.86.9.3257

Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt lymphoma.

E Shtivelman 1, B Henglein 1, P Groitl 1, M Lipp 1, J M Bishop 1
PMCID: PMC287109  PMID: 2470097

Abstract

Chromosomal translocations in Burkitt lymphoma and mouse plasmacytomas typically lie within or near the protooncogene MYC. In some instances, however, these tumors contain variant translocations with breakpoints located more distant from and downstream of MYC, in a domain commonly known as pvt-1. Until now, there has been no evidence that pvt-1 marks the location of a functional gene. Here we report the identification of a large transcriptional unit in human DNA that includes pvt-1. We have designated this unit as PVT. PVT begins 57 kilobase pairs downstream of MYC and occupies a minimum of 200 kilobase pairs of DNA. Some of the translocations that occur downstream of MYC in Burkitt lymphoma transect PVT; others lie between the two genes. None of the translocations we have studied appear to enhance transcription from an intact allele of PVT (indeed, they may inactivate that transcription), but some are associated with the production of abundant and anomalous 0.8- to 1.0-kilobase RNAs that contain the 5' exon of PVT and sequences transcribed from the constant region of an immunoglobulin gene (the reciprocal participant in the translocation). Identification of PVT should facilitate the exploration of how translocations downstream of MYC and insertions of retroviral DNA in the vicinity of pvt-1 might contribute to tumorigenesis.

Full text

PDF
3257

Images in this article

3259Image
on p.3259
3259Image
on p.3259

Selected References

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

  1. Bishop J. M. Cellular oncogenes and retroviruses. Annu Rev Biochem. 1983;52:301–354. doi: 10.1146/annurev.bi.52.070183.001505. [DOI] [PubMed] [Google Scholar]
  2. Cole M. D. The myc oncogene: its role in transformation and differentiation. Annu Rev Genet. 1986;20:361–384. doi: 10.1146/annurev.ge.20.120186.002045. [DOI] [PubMed] [Google Scholar]
  3. Cory S. Activation of cellular oncogenes in hemopoietic cells by chromosome translocation. Adv Cancer Res. 1986;47:189–234. doi: 10.1016/s0065-230x(08)60200-6. [DOI] [PubMed] [Google Scholar]
  4. Cory S., Graham M., Webb E., Corcoran L., Adams J. M. Variant (6;15) translocations in murine plasmacytomas involve a chromosome 15 locus at least 72 kb from the c-myc oncogene. EMBO J. 1985 Mar;4(3):675–681. doi: 10.1002/j.1460-2075.1985.tb03682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Dyson P. J., Rabbitts T. H. Chromatin structure around the c-myc gene in Burkitt lymphomas with upstream and downstream translocation points. Proc Natl Acad Sci U S A. 1985 Apr;82(7):1984–1988. doi: 10.1073/pnas.82.7.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Graham M., Adams J. M. Chromosome 8 breakpoint far 3' of the c-myc oncogene in a Burkitt's lymphoma 2;8 variant translocation is equivalent to the murine pvt-1 locus. EMBO J. 1986 Nov;5(11):2845–2851. doi: 10.1002/j.1460-2075.1986.tb04578.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham M., Adams J. M., Cory S. Murine T lymphomas with retroviral inserts in the chromosomal 15 locus for plasmacytoma variant translocations. 1985 Apr 25-May 1Nature. 314(6013):740–743. doi: 10.1038/314740a0. [DOI] [PubMed] [Google Scholar]
  11. Hartl P., Lipp M. Generation of a variant t(2;8) translocation of Burkitt's lymphoma by site-specific recombination via the kappa light-chain joining signals. Mol Cell Biol. 1987 Jun;7(6):2037–2045. doi: 10.1128/mcb.7.6.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Lemay G., Jolicoeur P. Rearrangement of a DNA sequence homologous to a cell-virus junction fragment in several Moloney murine leukemia virus-induced rat thymomas. Proc Natl Acad Sci U S A. 1984 Jan;81(1):38–42. doi: 10.1073/pnas.81.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lenoir G. M., Preud'homme J. L., Bernheim A., Berger R. Correlation between immunoglobulin light chain expression and variant translocation in Burkitt's lymphoma. Nature. 1982 Jul 29;298(5873):474–476. doi: 10.1038/298474a0. [DOI] [PubMed] [Google Scholar]
  15. Magrath I., Erikson J., Whang-Peng J., Sieverts H., Armstrong G., Benjamin D., Triche T., Alabaster O., Croce C. M. Synthesis of kappa light chains by cell lines containing an 8;22 chromosomal translocation derived from a male homosexual with Burkitt's lymphoma. Science. 1983 Dec 9;222(4628):1094–1098. doi: 10.1126/science.6316501. [DOI] [PubMed] [Google Scholar]
  16. Mengle-Gaw L., Rabbitts T. H. A human chromosome 8 region with abnormalities in B cell, HTLV-I+ T cell and c-myc amplified tumours. EMBO J. 1987 Jul;6(7):1959–1965. doi: 10.1002/j.1460-2075.1987.tb02458.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rooney C. M., Gregory C. D., Rowe M., Finerty S., Edwards C., Rupani H., Rickinson A. B. Endemic Burkitt's lymphoma: phenotypic analysis of tumor biopsy cells and of derived tumor cell lines. J Natl Cancer Inst. 1986 Sep;77(3):681–687. doi: 10.1093/jnci/77.3.681. [DOI] [PubMed] [Google Scholar]
  18. Schwab M., Klempnauer K. H., Alitalo K., Varmus H., Bishop M. Rearrangement at the 5' end of amplified c-myc in human COLO 320 cells is associated with abnormal transcription. Mol Cell Biol. 1986 Jul;6(7):2752–2755. doi: 10.1128/mcb.6.7.2752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Shtivelman E., Bishop J. M. The PVT gene frequently amplifies with MYC in tumor cells. Mol Cell Biol. 1989 Mar;9(3):1148–1154. doi: 10.1128/mcb.9.3.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sun L. K., Showe L. C., Croce C. M. Analysis of the 3' flanking region of the human c-myc gene in lymphomas with the t(8;22) and t(2;8) chromosomal translocations. Nucleic Acids Res. 1986 May 27;14(10):4037–4050. doi: 10.1093/nar/14.10.4037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Varmus H. E. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. doi: 10.1146/annurev.ge.18.120184.003005. [DOI] [PubMed] [Google Scholar]
  23. Villeneuve L., Rassart E., Jolicoeur P., Graham M., Adams J. M. Proviral integration site Mis-1 in rat thymomas corresponds to the pvt-1 translocation breakpoint in murine plasmacytomas. Mol Cell Biol. 1986 May;6(5):1834–1837. doi: 10.1128/mcb.6.5.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Webb E., Adams J. M., Cory S. Variant (6 ; 15) translocation in a murine plasmacytoma occurs near an immunoglobulin kappa gene but far from the myc oncogene. Nature. 1984 Dec 20;312(5996):777–779. doi: 10.1038/312777a0. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES