Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma


We have determined that PAX3 (found previously to be mutated in Waardenburg syndrome) is the chromosome 2 locus rearranged by the t(2;13)(q35;q14) translocation of the paediatric solid tumour alveolar rhabdomyosarcoma. The rearrangement breakpoints occur within an intron downstream of the paired box and homeodomain–encodingregions. Upstream PAX3 sequences hybridize to a novel transcript in t(2;13)–containing lines. Cloning and characterization of this novel transcript indicate that the translocation juxtaposes the PAX3 DNA binding elements with chromosome 13 sequences, suggesting formation of a hybrid transcription factor. Therefore, PAX3 gene alterations are associated with two completely unrelated human diseases.

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  1. 1

    Douglass, E.C. et al. A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet. Cell Genet. 45, 148–155 (1987).

  2. 2

    Turc-Carel, C. et al. Consistent chromosomal translocation in alveolar rhabdomyosarcoma. Cancer Genet. Cytogenet. 19, 361–362 (1986).

  3. 3

    Wang-Wuu, S., Soukup, S., Ballard, E., Gotwals, B. & Lampkin, B. Chromosomal analysis of sixteen human rhabdomyosarcomas. Cancer Res. 48, 983–987 (1988).

  4. 4

    Barr, F.G., Biegel, J.A., Sellinger, B., Womer, R. & Emanuel, B.S. Molecular and cytogenetic analysis of chromosomal arms 2q and 13q in alveolar rhabdomyosarcoma. Genes Chrom. Cancer 3, 153–161 (1991).

  5. 5

    Barr, F.G., Sellinger, B. & Emanuel, B.S. Localization of the rhabdomyosarcoma t(2;13) breakpoint on a physical map of chromosome 13. Genomics 11, 941–947 (1991).

  6. 6

    Barr, F.G., Holick, J., Nycum, L., Biegel, J.A. & Emanuel, B.S. Localization of the t(2;13) breakpoint of alveolar rhabdomyosarcoma on a physical map of chromosome 2. Genomics 13, 1150–1156 (1992).

  7. 7

    Mitchell, C.D., Ventris, J.A., Warr, T.J. & Cowell, J.K. Molecular definition in a somatic cell hybrid of a specific 2:13 translocation breakpoint in childhood rhabdomyosarcoma. Oncogene 6, 89–92 (1991).

  8. 8

    Shapiro, D.N. et al. Chromosomal sublocalization of the 2;13 translocation breakpoint in alveolar rhabdomyosarcoma. Genes Chrom. Cancer 4, 241–249 (1992).

  9. 9

    Burri, M., Tromvoukis, Y., Bopp, D., Frigerio, G. & Noll, M. Conservation of the paired domain in metazoans and its structure in three isolated human genes. EMBO J. 8, 1183–1190 (1989).

  10. 10

    Goulding, M.D., Chalepakis, G., Deutsch, U., Erselius, J.R. & Gruss, P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J. 10, 1135–1147 (1991).

  11. 11

    Epstein, D.J., Vekemans, M. & Gros, P. splotch (Sp2H), a mutation affecting development of the mouse neural tube, shows a deletion within the paired homeodomain of Pax-3. Cell 67, 767–774 (1991).

  12. 12

    Schurr, E., Skamene, E., Morgan, K., Chu, M.L. & Gros, P. Mapping of Col3a1 and Col6a3 to proximal murine chromosome 1 identifies conserved linkage of structural protein genes between murine chromosome 1 and human chromosome 2q. Genomics 8, 477–486 (1990).

  13. 13

    Malo, D. et al. The host resistance locus Bcg is tightly linked to a group of cytoskeleton-associated protein genes that include villin and desmin. Genomics 10, 356–364 (1991).

  14. 14

    Farrer, L.A. et al. Waardenburg syndrome (WS) Type I is caused by defects at multiple loci, one of which is near ALPP on chromosome 2: First report of the WS Consortium. Am. J. hum. Genet. 50, 902–913 (1992).

  15. 15

    Tassabehji, M. et al. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature 355, 635–636 (1992).

  16. 16

    Baldwin, C.T., Hoth, C.F., Amos, J.A., da-Silva, E.O. & An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome. Nature 355, 637–638 (1992).

  17. 17

    Morell, R. et al. A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family. Hum. molec. Genet. 1, 243–247 (1992).

  18. 18

    Tsukamoto, K. et al. Cloning and characterization of the inversion breakpoint at chromosome 2q35 in a patient with Waardenburg syndrome type I. Hum. molec. Genet. 1, 315–317 (1992).

  19. 19

    Delattre, O. et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 359, 162–165 (1992).

  20. 20

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

  21. 21

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

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