Abstract
HUMAN myxoid liposarcomas contain a characteristic chromosomal translocation, t(12;16)(ql3;pll)1,2, that is associated with a structural rearrangement of the gene encoding CHOP 3, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors4,5 residing on 12ql3.16. Using a CHOP-specifie complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS7, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.
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References
Turc-Carel, C. et al. Cancer Genet. Cytogenet. 23, 291–299 (1986).
Sreekantiaiah, S., Karakousis, C. P., Leong, S. P. L. & Sandberg, A. A. Cancer 69, 2484–2495 (1992).
Åman, P. et al. Genes Chrom. Cancer 5, 271–277 (1992).
Fornace, A. J. et al. Molec. cell. Biol. 9, 4196–4203 (1989).
Ron, D. & Habener, J. F. Genes Dev. 6, 439–453 (1992).
Park, J. S. et al. Gene 116, 259–267 (1992).
Delattre, O. et al. Nature 359, 162–165 (1992).
Kenan, D. J., Query, C. C. & Keene, J. D. Trends biochem. Sci. 16, 214–220 (1991).
Haynes, S. R., Rebbert, M. L., Mozer, B. A., Forquignon, F. & Dawid, I. B. Proc. natn. Acad. Sci. U.S.A. 84, 1819–1823 (1987).
Kiledjian, M. & Dryfuss, G. EMBO J. 11, 2655–2664 (1992).
Mitchell, P. J. & Tjian, R. Science 245, 371–378 (1989).
Ghisolfi, L., Joseph, G., Amalric, F. & Erard, M. J. biol. Chem. 267, 2955–2959 (1992).
Cao, Z., Umek, R. M. & McKnight, S. L. Genes Dev. 5, 1538–1552 (1991).
Carlson, S. G., Fawcett, T. W., Bartlett, J. D., Bernier, M. & Holbrook, N. J. Molec. cell. Biol. (in the press).
Frohman, M. A., Dush, M. K. & Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 85, 8998–9002 (1988).
Bugler, B. et al. J. biol. Chem. 262, 10922–10925 (1987).
Sachs, A. B., Bond, M. W. & Kornberg, R. D. Cell 45, 827–835 (1986).
Cretin, C. & Puigdomenech, P. Pl. molec. Biol. 15, 783–785 (1990).
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Crozat, A., Åman, P., Mandahl, N. et al. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature 363, 640–644 (1993). https://doi.org/10.1038/363640a0
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DOI: https://doi.org/10.1038/363640a0
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