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Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma

Nature Genetics volume 4, pages 175–180 (1993)Cite this article

Abstract

The search for tumour–specific markers is one of the chief goals in cancer biology. We show that the translocation t(12;16)(q13:p11) in malignant myxoid liposarcoma can be a fusion of the CHOP dominant negative transcription factor gene with a novel gene, FUS, which can result in fusion of the FUS glycine–rich protein with the whole CHOP coding region. The data support the concept that protein fusion may commonly occur in solid tumours resulting in tumour–specific markers of potential clinical importance. The data also indicate the importance of transcription disruption in the pathogenesis of solid tumours.

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References

  1. Nowell, P.C. & Hungerford, D.A. A minute chromosome in human chronic granulocytic leukaemia. Science 132, 1497 (1960).

    Google Scholar 

  2. Mitelman, F. Catalogue of Chromosome Aberrations in Cancer. (Wiley-Liss, New York, 1991).

    Google Scholar 

  3. Heim, S. & Mitelman, F. Cytogenetics of solid tumours. Rec. Adv. Path. 3, 37–66 (1991).

    Google Scholar 

  4. de Klein, A. et al. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature 300, 765–767 (1982).

    Article  CAS  Google Scholar 

  5. Bartram, C.R. et al. Translocation of c-abl oncogene with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 306, 277–280 (1983).

    Article  CAS  Google Scholar 

  6. Groffen, J. et al. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36, 93–99 (1984).

    Article  CAS  Google Scholar 

  7. Taub, R. et al. Translocation of the c-myc gene into the immunoglobulin heavy chain locus in human Burkitt's lymphoma and murine plasmacytoma cells. Proc. natn. Acad. Sci. U.S.A. 79, 7837–7841 (1982).

    Article  CAS  Google Scholar 

  8. Dalla-Favera, R. et al. Human c-myc oncogene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc. natn. Acad. Sci. U.S.A. 79, 7824–7827 (1982).

    Article  CAS  Google Scholar 

  9. Hamlyn, P.H. & Rabbitts, T.H. Translocation joins c-myc and immunoglobulin γl genes in a Burkitt's lymphoma revealing a third exon in the c-myc oncogene. Nature 304, 135–139 (1983).

    Article  CAS  Google Scholar 

  10. Davis, M., Malcolm, S. & Rabbitts, T.H. Chromosome translocation can occur on either side of the c-myc oncogene in Burkitt lymphoma. Nature 308, 286–288 (1984).

    Article  CAS  Google Scholar 

  11. Taub, R. et al. A novel alteration in the structure of an activated c-myc gene in a variant t(2;8) Burkitt lymphoma. Cell 37, 511–520 (1984).

    Article  CAS  Google Scholar 

  12. Croce, C.M. et al. Transcriptional activation of an unrearranged and untranslocated c-myc oncogene by translocation of a Cλ, locus in Burkitt lymphoma cells. Proc. natn. Acad. Sci. U.S.A. 80, 6922–6926 (1983).

    Article  CAS  Google Scholar 

  13. Rabbitts, T.H. Translocations, master genes, and differences between the origins of acute and chronic leukaemias. Cell 67, 641–644 (1991).

    Article  CAS  Google Scholar 

  14. Cleary, M.L. Oncogenic conversion of transcription factors by chromosomal translocations. Cell 66, 619–622 (1991).

    Article  CAS  Google Scholar 

  15. Kamps, M.P. et al. A new homeobox gene contributes the DNA binding domains of the t(1 ;19) translocation protein in pre-B ALL. Cell 60, 547–555 (1990).

    Article  CAS  Google Scholar 

  16. Nourse, J. et al. Chromosomal translocation t(1; 19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 60, 535–545 (1990).

    Article  CAS  Google Scholar 

  17. Borrow, J., Goddard, A.D., Sheer, D. & Solomon, E. Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17. Science 249, 451–458 (1990).

    Article  Google Scholar 

  18. de The, H., Chomienne, C., Lanotte, M., Degos, L. & Dejean, A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus. Nature 347, 558–561 (1990).

    Article  CAS  Google Scholar 

  19. Alcalay, M. et al. Translocation breakpoint of acute promyelocytic leukaemia lies within the retinoic acid receptor α locus. Proc. natn. Acad. Sci. U.S.A. 88, 1977–1981 (1991).

    Article  CAS  Google Scholar 

  20. Erickson, P. et al. Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript AML-1/ETO, with similarity to Drosophila segmentation gene, runt. Blood 80, 1825–1831 (1992).

    CAS  PubMed  Google Scholar 

  21. Miyoshi, H. et al. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript EMBO J. (in the press).

  22. von Lindern, M. et al. The translocation (6;9) associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric leukemia-specific dek-can mRNA. Molec. cell. Biol. 12, 1687–1697 (1992).

    Article  CAS  Google Scholar 

  23. Delattre, O. et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 359, 162–164 (1992).

    Article  CAS  Google Scholar 

  24. Aman, P. et al. Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Genes, Chrom. Cancer 5, 278–285 (1992).

    Article  CAS  Google Scholar 

  25. Ron, D. & Habener, J.F. CHOP, a novel developmentally regulated nuclear protein that dimerises with transcription factors C/EBP and LAP and functions as a dominat-negative inhibitor of gene transcription. Genes Dev. 6, 439–453 (1992).

    Article  CAS  Google Scholar 

  26. Park, J.S. et al. Isolation, characterisation and chromosomal localisation of the human GADD153 gene. Gene 116, 259–267 (1992).

    Article  CAS  Google Scholar 

  27. Eneroth, M. et al. Localisation of the chromosome breakpoints of the t(12;16) in liposarcomas to sub-bands 12q 13.3 and 16p11.2. Cancer Genet. Cytogent. 48, 101–107 (1990).

    Article  CAS  Google Scholar 

  28. Dube, I.D. et al. A novel human homeobox gene lies at the chromosome 10 breakpoint in lymphoid neoplasias with chromosomal translocation t(10;14). Blood 78, 2992–3003 (1991).

    Google Scholar 

  29. Kennedy, M. et al. HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24. Proc. natn. Acad. Sci. U.S.A. 88, 8900–8904 (1991).

    Article  CAS  Google Scholar 

  30. Hatano, M., Roberts, C.W.M., Minden, M., Crist, W.M. & Korsmeyer, S.J. Deregulation of a homeobox gene, HOX11, bythet(10;14) in T cell leukaemia. Science 253, 70–82 (1991).

    Article  Google Scholar 

  31. Lu, M., Gong, Z., Shen, W. & Ho, A.D. The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukaemia codes for a homeobox protein. EMBO J. 10, 2905–2910 (1991).

    Article  CAS  Google Scholar 

  32. Rieger, M. & Franke, W.W. Identification of an orthologous mammalian cytokeratin gene. J. molec. Biol. 204, 841–856 (1988).

    Article  CAS  Google Scholar 

  33. Mitchell, P.J. & Tijan, R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science 245, 371–378 (1989).

    Article  CAS  Google Scholar 

  34. Rabbitts, T.H. & Boehm, T. Structural and functional chimerism results from chromosomal translocation in lymphoid tumours. Adv. Imm. 50, 119–146 (1991).

    Article  CAS  Google Scholar 

  35. Barr, F.G. et al. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nature Genet. 3, 113–117 (1993).

    Article  CAS  Google Scholar 

  36. Trent, J.M. & Meltzer, P.S. The last shall be first. Nature Genet. 3, 101–102 (1993).

    Article  CAS  Google Scholar 

  37. Southern, E.M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  38. Feinberg, A.P. & Vogelstein, B. A technique for radiolabelling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13 (1983).

    Article  CAS  Google Scholar 

  39. Buroker, N.E. et al. Four restriction fragment length polymorphisms revealed by probes from a single cosmid map to human chromosome 12q. Hum. Genet. 72, 86–91 (1986).

    Article  CAS  Google Scholar 

  40. Spurr, N.K. & Rooke, L. Confirmation of assignment of vitronectin and fibronectin receptor α-subunits. Ann. hum. Genet. 55, 217–223 (1991).

    Article  CAS  Google Scholar 

  41. Povey, S. et al. Assignment of the human locus defining phosphoglycolate phosphotase to chromosome 16. Ann. hum. Genet. 43, 241–248 (1980).

    Article  CAS  Google Scholar 

  42. Mulley, J.C. & Callen, D.F. New regional localisation for HAGH and PGP on human chromosome 16. Ann. Genet. 29, 235–241 (1986).

    Google Scholar 

  43. Thomas, P.S. Hybridisation of denatured RNA and small DNA frgaments transferred to nitrocellulose. Proc. natn. Acad. Sci. U.S.A. 77, 5201–5205 (1980).

    Article  CAS  Google Scholar 

  44. Bankier, A.T. & Barrell, B.G. Shotgun DNA sequencing methods in Nucleic Acid Sequencing, (eds Howe, C. J. & Wards, E.S.) 78 (IRL Press, Oxford, 1989).

    Google Scholar 

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Authors and Affiliations

  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

    T.H. Rabbitts, A. Forster, R. Larson & P. Nathan

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  1. T.H. Rabbitts
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  2. A. Forster
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  3. R. Larson
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  4. P. Nathan
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Rabbitts, T., Forster, A., Larson, R. et al. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet 4, 175–180 (1993). https://doi.org/10.1038/ng0693-175

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