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. 1987 Jun 11;15(11):4553–4565. doi: 10.1093/nar/15.11.4553

Clustered somatic mutations in and around first exon of non-rearranged c-myc in Burkitt lymphoma with t(8;22) translocation.

M F Szajnert, S Saule, G W Bornkamm, H Wajcman, G M Lenoir, J C Kaplan
PMCID: PMC340879  PMID: 3035497

Abstract

We have examined the restriction map of the c-myc gene in 15 BL cell lines carrying the variant t(8;22) translocation in which c-myc is known to remain on chromosome 8. Using 3 restriction enzymes cutting outside the c-myc domain (EcoRI, BamHI, HindIII), we found no evidence for a c-myc/Ig lambda rearrangement in 14 BL cell lines. In the last one, BL 37, the 3' flanking region was rearranged corresponding to the already identified breakpoint located 400 pb downstream from the c-myc gene (9). Using 4 restriction enzymes cutting inside the c-myc gene (PvuII, PstI, SacI, HincII) we looked for discrete abnormalities within the gene limits, and we found in 9 BL cell lines several abolished and created sites, compatible with multiple independent somatic mutations. They are significantly clustered in the 5' non coding region, with a striking prevalence at the end of exon 1. The role of mutations in the non-coding first exon region for the deregulation of c-myc expression is discussed.

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Selected References

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

  1. 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]
  2. Bentley D. L., Groudine M. A block to elongation is largely responsible for decreased transcription of c-myc in differentiated HL60 cells. Nature. 1986 Jun 12;321(6071):702–706. doi: 10.1038/321702a0. [DOI] [PubMed] [Google Scholar]
  3. Carè A., Cianetti L., Giampaolo A., Sposi N. M., Zappavigna V., Mavilio F., Alimena G., Amadori S., Mandelli F., Peschle C. Translocation of c-myc into the immunoglobulin heavy-chain locus in human acute B-cell leukemia. A molecular analysis. EMBO J. 1986 May;5(5):905–911. doi: 10.1002/j.1460-2075.1986.tb04302.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Dani C., Blanchard J. M., Piechaczyk M., El Sabouty S., Marty L., Jeanteur P. Extreme instability of myc mRNA in normal and transformed human cells. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7046–7050. doi: 10.1073/pnas.81.22.7046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Darveau A., Pelletier J., Sonenberg N. Differential efficiencies of in vitro translation of mouse c-myc transcripts differing in the 5' untranslated region. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2315–2319. doi: 10.1073/pnas.82.8.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Denny C. T., Hollis G. F., Magrath I. T., Kirsch I. R. Burkitt lymphoma cell line carrying a variant translocation creates new DNA at the breakpoint and violates the hierarchy of immunoglobulin gene rearrangement. Mol Cell Biol. 1985 Nov;5(11):3199–3207. doi: 10.1128/mcb.5.11.3199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dunnick W., Shell B. E., Dery C. DNA sequences near the site of reciprocal recombination between a c-myc oncogene and an immunoglobulin switch region. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7269–7273. doi: 10.1073/pnas.80.23.7269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Eick D., Bornkamm G. W. Transcriptional arrest within the first exon is a fast control mechanism in c-myc gene expression. Nucleic Acids Res. 1986 Nov 11;14(21):8331–8346. doi: 10.1093/nar/14.21.8331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eick D., Piechaczyk M., Henglein B., Blanchard J. M., Traub B., Kofler E., Wiest S., Lenoir G. M., Bornkamm G. W. Aberrant c-myc RNAs of Burkitt's lymphoma cells have longer half-lives. EMBO J. 1985 Dec 30;4(13B):3717–3725. doi: 10.1002/j.1460-2075.1985.tb04140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gazin C., Dupont de Dinechin S., Hampe A., Masson J. M., Martin P., Stehelin D., Galibert F. Nucleotide sequence of the human c-myc locus: provocative open reading frame within the first exon. EMBO J. 1984 Feb;3(2):383–387. doi: 10.1002/j.1460-2075.1984.tb01816.x. [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. 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]
  14. Leder P., Battey J., Lenoir G., Moulding C., Murphy W., Potter H., Stewart T., Taub R. Translocations among antibody genes in human cancer. Science. 1983 Nov 18;222(4625):765–771. doi: 10.1126/science.6356357. [DOI] [PubMed] [Google Scholar]
  15. Murphy W., Sarid J., Taub R., Vasicek T., Battey J., Lenoir G., Leder P. A translocated human c-myc oncogene is altered in a conserved coding sequence. Proc Natl Acad Sci U S A. 1986 May;83(9):2939–2943. doi: 10.1073/pnas.83.9.2939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pelicci P. G., Knowles D. M., 2nd, Magrath I., Dalla-Favera R. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1986 May;83(9):2984–2988. doi: 10.1073/pnas.83.9.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Piechaczyk M., Yang J. Q., Blanchard J. M., Jeanteur P., Marcu K. B. Posttranscriptional mechanisms are responsible for accumulation of truncated c-myc RNAs in murine plasma cell tumors. Cell. 1985 Sep;42(2):589–597. doi: 10.1016/0092-8674(85)90116-3. [DOI] [PubMed] [Google Scholar]
  18. Rabbitts P. H., Forster A., Stinson M. A., Rabbitts T. H. Truncation of exon 1 from the c-myc gene results in prolonged c-myc mRNa stability. EMBO J. 1985 Dec 30;4(13B):3727–3733. doi: 10.1002/j.1460-2075.1985.tb04141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. Remmers E. F., Yang J. Q., Marcu K. B. A negative transcriptional control element located upstream of the murine c-myc gene. EMBO J. 1986 May;5(5):899–904. doi: 10.1002/j.1460-2075.1986.tb04301.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Showe L. C., Ballantine M., Nishikura K., Erikson J., Kaji H., Croce C. M. Cloning and sequencing of a c-myc oncogene in a Burkitt's lymphoma cell line that is translocated to a germ line alpha switch region. Mol Cell Biol. 1985 Mar;5(3):501–509. doi: 10.1128/mcb.5.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. 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]
  27. Wiman K. G., Clarkson B., Hayday A. C., Saito H., Tonegawa S., Hayward W. S. Activation of a translocated c-myc gene: role of structural alterations in the upstream region. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6798–6802. doi: 10.1073/pnas.81.21.6798. [DOI] [PMC free article] [PubMed] [Google Scholar]

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