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. 1988 Dec;85(23):9171–9175. doi: 10.1073/pnas.85.23.9171

Analysis of a T-cell tumor-specific breakpoint cluster at human chromosome 14q32.

L Mengle-Gaw 1, D G Albertson 1, P D Sherrington 1, T H Rabbitts 1
PMCID: PMC282689  PMID: 3194418

Abstract

Cytogenetic abnormalities involving chromosome 14 band q32 are consistently observed in human T-cell tumors. Patients with ataxia-telangiectasia (AT) are especially prone to development of these tumors, which frequently carry either inversion inv(14)(q11;q32) or translocation t(14;14) (q11;q32) chromosomes. We have previously shown that the cytogenetic breakpoints of one t(14;14)(q11;q32) chromosome and two inv(14)(q11;q32) chromosomes in T-cell tumors from AT and non-AT patients join the T-cell receptor alpha chain locus, at chromosome band 14q11, with a region(s) at 14q32 centromeric of the immunoglobulin heavy chain variable region (VH) gene IGHV. We now show that these two inv(14) breakpoints are linked by 2.1 kb of germ-line 14q32 DNA and that the three breakpoints define, by in situ hybridization analysis, a single locus at chromosome band 14q32.1 located about 15-20 million base pairs on the centromeric side of the IGH locus. Sequence analysis of the 14q32.1 breakpoint regions indicates that abnormal recombination does not universally result from mistaken V-D-J joining (D = diversity region; J = joining region). Therefore, we invoke a tumor selection model to describe the role of the 14q32.1 locus in tumor development.

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Selected References

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

  1. Albertson D. G. Localization of the ribosomal genes in Caenorhabditis elegans chromosomes by in situ hybridization using biotin-labeled probes. EMBO J. 1984 Jun;3(6):1227–1234. doi: 10.1002/j.1460-2075.1984.tb01957.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Albertson D. G. Mapping muscle protein genes by in situ hybridization using biotin-labeled probes. EMBO J. 1985 Oct;4(10):2493–2498. doi: 10.1002/j.1460-2075.1985.tb03961.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aurias A., Croquette M. F., Nuyts J. P., Griscelli C., Dutrillaux B. New data on clonal anomalies of chromosome 14 in ataxia telangiectasia: tct(14;14) and inv(14). Hum Genet. 1986 Jan;72(1):22–24. doi: 10.1007/BF00278811. [DOI] [PubMed] [Google Scholar]
  4. Baer R., Chen K. C., Smith S. D., Rabbitts T. H. Fusion of an immunoglobulin variable gene and a T cell receptor constant gene in the chromosome 14 inversion associated with T cell tumors. Cell. 1985 Dec;43(3 Pt 2):705–713. doi: 10.1016/0092-8674(85)90243-0. [DOI] [PubMed] [Google Scholar]
  5. Baer R., Forster A., Rabbitts T. H. The mechanism of chromosome 14 inversion in a human T cell lymphoma. Cell. 1987 Jul 3;50(1):97–105. doi: 10.1016/0092-8674(87)90666-0. [DOI] [PubMed] [Google Scholar]
  6. Baer R., Heppell A., Taylor A. M., Rabbitts P. H., Boullier B., Rabbitts T. H. The breakpoint of an inversion of chromosome 14 in a T-cell leukemia: sequences downstream of the immunoglobulin heavy chain locus are implicated in tumorigenesis. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9069–9073. doi: 10.1073/pnas.84.24.9069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bridges B. A., Harnden D. G. Untangling ataxia-telangiectasia. Nature. 1981 Jan 22;289(5795):222–223. doi: 10.1038/289222a0. [DOI] [PubMed] [Google Scholar]
  8. Clare N., Boldt D., Messerschmidt G., Zeltzer P., Hansen K., Manhoff L. Lymphocyte malignancy and chromosome 14: structural aberrations involving band q11. Blood. 1986 Mar;67(3):704–709. [PubMed] [Google Scholar]
  9. Davey M. P., Bertness V., Nakahara K., Johnson J. P., McBride O. W., Waldmann T. A., Kirsch I. R. Juxtaposition of the T-cell receptor alpha-chain locus (14q11) and a region (14q32) of potential importance in leukemogenesis by a 14;14 translocation in a patient with T-cell chronic lymphocytic leukemia and ataxia-telangiectasia. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9287–9291. doi: 10.1073/pnas.85.23.9287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Denny C. T., Hollis G. F., Hecht F., Morgan R., Link M. P., Smith S. D., Kirsch I. R. Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development. Science. 1986 Oct 10;234(4773):197–200. doi: 10.1126/science.3092355. [DOI] [PubMed] [Google Scholar]
  11. Denny C. T., Yoshikai Y., Mak T. W., Smith S. D., Hollis G. F., Kirsch I. R. A chromosome 14 inversion in a T-cell lymphoma is caused by site-specific recombination between immunoglobulin and T-cell receptor loci. Nature. 1986 Apr 10;320(6062):549–551. doi: 10.1038/320549a0. [DOI] [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Hecht F., Hecht B. K., Kirsch I. R. Fragile sites limited to lymphocytes: molecular recombination and malignancy. Cancer Genet Cytogenet. 1987 May;26(1):95–104. doi: 10.1016/0165-4608(87)90137-3. [DOI] [PubMed] [Google Scholar]
  15. Kennaugh A. A., Butterworth S. V., Hollis R., Baer R., Rabbitts T. H., Taylor A. M. The chromosome breakpoint at 14q32 in an ataxia telangiectasia t(14;14) T cell clone is different from the 14q32 breakpoint in Burkitts and an inv(14) T cell lymphoma. Hum Genet. 1986 Jul;73(3):254–259. doi: 10.1007/BF00401239. [DOI] [PubMed] [Google Scholar]
  16. Krawinkel U., Rabbitts T. H. Comparison of the hinge-coding segments in human immunoglobulin gamma heavy chain genes and the linkage of the gamma 2 and gamma 4 subclass genes. EMBO J. 1982;1(4):403–407. doi: 10.1002/j.1460-2075.1982.tb01182.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. LeFranc M. P., Forster A., Baer R., Stinson M. A., Rabbitts T. H. Diversity and rearrangement of the human T cell rearranging gamma genes: nine germ-line variable genes belonging to two subgroups. Cell. 1986 Apr 25;45(2):237–246. doi: 10.1016/0092-8674(86)90388-0. [DOI] [PubMed] [Google Scholar]
  18. Matthyssens G., Rabbitts T. H. Structure and multiplicity of genes for the human immunoglobulin heavy chain variable region. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6561–6565. doi: 10.1073/pnas.77.11.6561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Mengle-Gaw L., Willard H. F., Smith C. I., Hammarström L., Fischer P., Sherrington P., Lucas G., Thompson P. W., Baer R., Rabbitts T. H. Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32. EMBO J. 1987 Aug;6(8):2273–2280. doi: 10.1002/j.1460-2075.1987.tb02501.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Russo G., Isobe M., Pegoraro L., Finan J., Nowell P. C., Croce C. M. Molecular analysis of a t(7;14)(q35;q32) chromosome translocation in a T cell leukemia of a patient with ataxia telangiectasia. Cell. 1988 Apr 8;53(1):137–144. doi: 10.1016/0092-8674(88)90495-3. [DOI] [PubMed] [Google Scholar]
  22. Sadamori N., Kusano M., Nishino K., Tagawa M., Yao E., Yamada Y., Amagasaki T., Kinoshita K., Ichimaru M. Abnormalities of chromosome 14 at band 14q11 in Japanese patients with adult T-cell leukemia. Cancer Genet Cytogenet. 1985 Jul;17(3):279–282. doi: 10.1016/0165-4608(85)90019-6. [DOI] [PubMed] [Google Scholar]
  23. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  24. Ueshima Y., Rowley J. D., Variakojis D., Winter J., Gordon L. Cytogenetic studies on patients with chronic T cell leukemia/lymphoma. Blood. 1984 May;63(5):1028–1038. [PubMed] [Google Scholar]
  25. Zech L., Godal T., Hammarström L., Mellstedt H., Smith C. I., Tötterman T., Went M. Specific chromosome markers involved with chronic T lymphocyte tumors. Cancer Genet Cytogenet. 1986 Mar 1;21(1):67–77. doi: 10.1016/0165-4608(86)90201-3. [DOI] [PubMed] [Google Scholar]

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