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
. 1990 Sep;87(18):6964–6968. doi: 10.1073/pnas.87.18.6964

Pvt-1 transcripts are found in normal tissues and are altered by reciprocal(6;15) translocations in mouse plasmacytomas.

K Huppi 1, D Siwarski 1, R Skurla 1, D Klinman 1, J F Mushinski 1
PMCID: PMC54662  PMID: 2402486

Abstract

The mouse Pvt-1 (for plasmacytoma variant translocation) region maps to a chromosome 15 breakpoint region that is frequently interrupted by "variant" reciprocal chromosome translocations, rcpt(6;15), in plasmacytomas. This region lies several hundred kilobases (kb) 3' of the mouse c-myc gene (Myc) which is deregulated in both rcpt(6;15) and rcpt(12;15) plasmacytomas. rcpt(12;15) translocations apparently activate c-myc directly by interrupting the gene itself, but the mechanism causing c-myc deregulation in tumors bearing rcpt(6;15) translocations remains unknown. The indirect activation of c-myc by Pvt-1 interruption has remained an appealing possibility, but heretofore it has not been possible to establish such a connection. Furthermore, no genes from the Pvt-1 locus have been shown to be transcribed in normal tissues or in tumors with rcpt(6;15) translocations. We report the isolation of a cDNA clone, Pvt-1-1, from mouse spleen mRNA that is specific to the Pvt-1 region. This cDNA probe detects low levels of large (ca. 14 kb) RNA transcripts in normal mouse tissues. In plasmacytomas with rcpt(6;15) translocations, the Pvt-1 transcripts are elevated in abundance and truncated in size. Both changes are apparently induced by the chromosomal translocation. Expression of 14-kb Pvt-1 RNA is elevated in B-cell tumor lines that express immunoglobulin light chain genes; thus, we postulate that these translocations are facilitated by the increased DNA accessibility of immunoglobulin kappa light chain and Pvt-1 genes when they are simultaneously expressed at certain times during B-cell ontogeny.

Full text

PDF
6964

Images in this article

6965Image
on p.6965
6965Image
on p.6965
6965Image
on p.6965
6965Image
on p.6965
6965Image
on p.6965
6967Image
on p.6967
6967Image
on p.6967

Selected References

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

  1. Banerjee M., Wiener F., Spira J., Babonits M., Nilsson M. G., Sumegi J., Klein G. Mapping of the c-myc, pvt-1 and immunoglobulin kappa genes in relation to the mouse plasmacytoma-associated variant (6;15) translocation breakpoint. EMBO J. 1985 Dec 1;4(12):3183–3188. doi: 10.1002/j.1460-2075.1985.tb04063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Banerjee M., Wiener F., Spira J., Babonits M., Nilsson M. G., Sumegi J., Klein G. Mapping of the c-myc, pvt-1 and immunoglobulin kappa genes in relation to the mouse plasmacytoma-associated variant (6;15) translocation breakpoint. EMBO J. 1985 Dec 1;4(12):3183–3188. doi: 10.1002/j.1460-2075.1985.tb04063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Citri Y., Braun J., Baltimore D. Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines. J Exp Med. 1987 Apr 1;165(4):1188–1194. doi: 10.1084/jem.165.4.1188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Citri Y., Braun J., Baltimore D. Elevated myc expression and c-myc amplification in spontaneously occurring B lymphoid cell lines. J Exp Med. 1987 Apr 1;165(4):1188–1194. doi: 10.1084/jem.165.4.1188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coleclough C., Perry R. P., Karjalainen K., Weigert M. Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression. Nature. 1981 Apr 2;290(5805):372–378. doi: 10.1038/290372a0. [DOI] [PubMed] [Google Scholar]
  6. Coleclough C., Perry R. P., Karjalainen K., Weigert M. Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression. Nature. 1981 Apr 2;290(5805):372–378. doi: 10.1038/290372a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Henglein B., Synovzik H., Groitl P., Bornkamm G. W., Hartl P., Lipp M. Three breakpoints of variant t(2;8) translocations in Burkitt's lymphoma cells fall within a region 140 kilobases distal from c-myc. Mol Cell Biol. 1989 May;9(5):2105–2113. doi: 10.1128/mcb.9.5.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huppi K., Duncan R., Potter M. Myc-1 is centromeric to the linkage group Ly-6--Sis--Gdc-1 on mouse chromosome 15. Immunogenetics. 1988;27(3):215–219. doi: 10.1007/BF00346589. [DOI] [PubMed] [Google Scholar]
  17. Huppi K., Duncan R., Potter M. Myc-1 is centromeric to the linkage group Ly-6--Sis--Gdc-1 on mouse chromosome 15. Immunogenetics. 1988;27(3):215–219. doi: 10.1007/BF00346589. [DOI] [PubMed] [Google Scholar]
  18. Kirsch I. R., Brown J. A., Lawrence J., Korsmeyer S. J., Morton C. C. Translocations that highlight chromosomal regions of differentiated activity. Cancer Genet Cytogenet. 1985 Oct;18(2):159–171. doi: 10.1016/0165-4608(85)90066-4. [DOI] [PubMed] [Google Scholar]
  19. Kirsch I. R., Brown J. A., Lawrence J., Korsmeyer S. J., Morton C. C. Translocations that highlight chromosomal regions of differentiated activity. Cancer Genet Cytogenet. 1985 Oct;18(2):159–171. doi: 10.1016/0165-4608(85)90066-4. [DOI] [PubMed] [Google Scholar]
  20. Koehne C. F., Lazo P. A., Alves K., Lee J. S., Tsichlis P. N., O'Donnell P. V. The Mlvi-1 locus involved in the induction of rat T-cell lymphomas and the pvt-1/Mis-1 locus are identical. J Virol. 1989 May;63(5):2366–2369. doi: 10.1128/jvi.63.5.2366-2369.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Mountz J. D., Steinberg A. D., Klinman D. M., Smith H. R., Mushinski J. F. Autoimmunity and increased c-myb transcription. Science. 1984 Nov 30;226(4678):1087–1089. doi: 10.1126/science.6494925. [DOI] [PubMed] [Google Scholar]
  23. Mountz J. D., Steinberg A. D., Klinman D. M., Smith H. R., Mushinski J. F. Autoimmunity and increased c-myb transcription. Science. 1984 Nov 30;226(4678):1087–1089. doi: 10.1126/science.6494925. [DOI] [PubMed] [Google Scholar]
  24. Mushinski J. F., Davidson W. F., Morse H. C., 3rd Activation of cellular oncogenes in human and mouse leukemia-lymphomas: spontaneous and induced oncogene expression in murine B lymphocytic neoplasms. Cancer Invest. 1987;5(4):345–368. [PubMed] [Google Scholar]
  25. Mushinski J. F., Davidson W. F., Morse H. C., 3rd Activation of cellular oncogenes in human and mouse leukemia-lymphomas: spontaneous and induced oncogene expression in murine B lymphocytic neoplasms. Cancer Invest. 1987;5(4):345–368. [PubMed] [Google Scholar]
  26. Scott C. L., Potter M. Polymorphism of C lambda genes and units of duplication in the genus Mus. J Immunol. 1984 May;132(5):2630–2637. [PubMed] [Google Scholar]
  27. Scott C. L., Potter M. Polymorphism of C lambda genes and units of duplication in the genus Mus. J Immunol. 1984 May;132(5):2630–2637. [PubMed] [Google Scholar]
  28. Shtivelman E., Bishop J. M. Effects of translocations on transcription from PVT. Mol Cell Biol. 1990 Apr;10(4):1835–1839. doi: 10.1128/mcb.10.4.1835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Shtivelman E., Henglein B., Groitl P., Lipp M., Bishop J. M. Identification of a human transcription unit affected by the variant chromosomal translocations 2;8 and 8;22 of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1989 May;86(9):3257–3260. doi: 10.1073/pnas.86.9.3257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thomas B. J., Rothstein R. Elevated recombination rates in transcriptionally active DNA. Cell. 1989 Feb 24;56(4):619–630. doi: 10.1016/0092-8674(89)90584-9. [DOI] [PubMed] [Google Scholar]
  32. Thomas B. J., Rothstein R. Elevated recombination rates in transcriptionally active DNA. Cell. 1989 Feb 24;56(4):619–630. doi: 10.1016/0092-8674(89)90584-9. [DOI] [PubMed] [Google Scholar]
  33. Tsichlis P. N., Shepherd B. M., Bear S. E. Activation of the Mlvi-1/mis1/pvt-1 locus in Moloney murine leukemia virus-induced T-cell lymphomas. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5487–5491. doi: 10.1073/pnas.86.14.5487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Yancopoulos G. D., Alt F. W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell. 1985 Feb;40(2):271–281. doi: 10.1016/0092-8674(85)90141-2. [DOI] [PubMed] [Google Scholar]
  37. Yancopoulos G. D., Alt F. W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell. 1985 Feb;40(2):271–281. doi: 10.1016/0092-8674(85)90141-2. [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