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. 1989 Jun;86(11):4161–4165. doi: 10.1073/pnas.86.11.4161

Clustering of breakpoints on chromosome 10 in acute T-cell leukemias with the t(10;14) chromosome translocation.

J Kagan 1, L R Finger 1, J Letofsky 1, J Finan 1, P C Nowell 1, C M Croce 1
PMCID: PMC287409  PMID: 2542965

Abstract

The T-cell receptor (TCR) alpha/delta chain locus on chromosome 14q11 is nonrandomly involved in translocations and inversions in human T-cell neoplasms. We have analyzed three acute T-lymphoblastic leukemia samples carrying a t(10;14)(q24;q11) chromosome translocation by means of somatic cell hybrids and molecular cloning. In all cases studied the translocation splits the TCR delta chain locus. Somatic cell hybrids containing the human 10q+ chromosome resulting from the translocation retain the human terminal deoxynucleotidyltransferase gene mapped at 10q23-q24 and the diversity and joining, D delta 2-J delta 1, regions of the TCR delta chain, but not the V alpha region (variable region of the TCR alpha chain), demonstrating that the split occurred within the V alpha-D delta 2 region. Molecular cloning of the breakpoint junctions revealed that the TCR delta chain sequences involved are made from the D delta 2 segment. The chromosome breakpoints are clustered within a region of approximately 263 base pairs of chromosome 10. The results suggest that the translocation of the TCR delta chain locus to a locus on 10q, which we have designated TCL3, results in deregulation of this putative oncogene, leading to acute T-cell leukemia.

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Selected References

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

  1. Boehm T., Baer R., Lavenir I., Forster A., Waters J. J., Nacheva E., Rabbitts T. H. The mechanism of chromosomal translocation t(11;14) involving the T-cell receptor C delta locus on human chromosome 14q11 and a transcribed region of chromosome 11p15. EMBO J. 1988 Feb;7(2):385–394. doi: 10.1002/j.1460-2075.1988.tb02825.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boehm T., Buluwela L., Williams D., White L., Rabbitts T. H. A cluster of chromosome 11p13 translocations found via distinct D-D and D-D-J rearrangements of the human T cell receptor delta chain gene. EMBO J. 1988 Jul;7(7):2011–2017. doi: 10.1002/j.1460-2075.1988.tb03040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chien Y. H., Iwashima M., Kaplan K. B., Elliott J. F., Davis M. M. A new T-cell receptor gene located within the alpha locus and expressed early in T-cell differentiation. 1987 Jun 25-Jul 1Nature. 327(6124):677–682. doi: 10.1038/327677a0. [DOI] [PubMed] [Google Scholar]
  4. Croce C. M., Isobe M., Palumbo A., Puck J., Ming J., Tweardy D., Erikson J., Davis M., Rovera G. Gene for alpha-chain of human T-cell receptor: location on chromosome 14 region involved in T-cell neoplasms. Science. 1985 Mar 1;227(4690):1044–1047. doi: 10.1126/science.3919442. [DOI] [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. Dubé I. D., Raimondi S. C., Pi D., Kalousek D. K. A new translocation, t(10;14)(q24;q11), in T cell neoplasia. Blood. 1986 Apr;67(4):1181–1184. [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. Erikson J., Williams D. L., Finan J., Nowell P. C., Croce C. M. Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias. Science. 1985 Aug 23;229(4715):784–786. doi: 10.1126/science.3875152. [DOI] [PubMed] [Google Scholar]
  10. Finger L. R., Harvey R. C., Moore R. C., Showe L. C., Croce C. M. A common mechanism of chromosomal translocation in T- and B-cell neoplasia. Science. 1986 Nov 21;234(4779):982–985. doi: 10.1126/science.3490692. [DOI] [PubMed] [Google Scholar]
  11. Finger L. R., Harvey R. C., Moore R. C., Showe L. C., Croce C. M. A common mechanism of chromosomal translocation in T- and B-cell neoplasia. Science. 1986 Nov 21;234(4779):982–985. doi: 10.1126/science.3490692. [DOI] [PubMed] [Google Scholar]
  12. Haluska F. G., Finver S., Tsujimoto Y., Croce C. M. The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining. Nature. 1986 Nov 13;324(6093):158–161. doi: 10.1038/324158a0. [DOI] [PubMed] [Google Scholar]
  13. Hata S., Brenner M. B., Krangel M. S. Identification of putative human T cell receptor delta complementary DNA clones. Science. 1987 Oct 30;238(4827):678–682. doi: 10.1126/science.3499667. [DOI] [PubMed] [Google Scholar]
  14. Hecht F., Morgan R., Hecht B. K., Smith S. D. Common region on chromosome 14 in T-cell leukemia and lymphoma. Science. 1984 Dec 21;226(4681):1445–1447. doi: 10.1126/science.6438800. [DOI] [PubMed] [Google Scholar]
  15. Isobe M., Huebner K., Erikson J., Peterson R. C., Bollum F. J., Chang L. M., Croce C. M. Chromosome localization of the gene for human terminal deoxynucleotidyltransferase to region 10q23-q25. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5836–5840. doi: 10.1073/pnas.82.17.5836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Isobe M., Russo G., Haluska F. G., Croce C. M. Cloning of the gene encoding the delta subunit of the human T-cell receptor reveals its physical organization within the alpha-subunit locus and its involvement in chromosome translocations in T-cell malignancy. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3933–3937. doi: 10.1073/pnas.85.11.3933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kagan J., Finan J., Letofsky J., Besa E. C., Nowell P. C., Croce C. M. Alpha-chain locus of the T-cell antigen receptor is involved in the t(10;14) chromosome translocation of T-cell acute lymphocytic leukemia. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4543–4546. doi: 10.1073/pnas.84.13.4543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  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. Tsujimoto Y., Jaffe E., Cossman J., Gorham J., Nowell P. C., Croce C. M. Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11;14) chromosome translocation. Nature. 1985 May 23;315(6017):340–343. doi: 10.1038/315340a0. [DOI] [PubMed] [Google Scholar]
  23. Yunis J. J. The chromosomal basis of human neoplasia. Science. 1983 Jul 15;221(4607):227–236. doi: 10.1126/science.6336310. [DOI] [PubMed] [Google Scholar]
  24. Zech L., Gahrton G., Hammarström L., Juliusson G., Mellstedt H., Robèrt K. H., Smith C. I. Inversion of chromosome 14 marks human T-cell chronic lymphocytic leukaemia. 1984 Apr 26-May 2Nature. 308(5962):858–860. doi: 10.1038/308858a0. [DOI] [PubMed] [Google Scholar]

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