| Hybrid Gene |
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| Generation of chimeric genes by the 2;2 translocation in ARMS. The exons of the wild-type and fusion genes are shown as boxes above each map and the translocation breakpoint distributions are shown as line segments below the map of the wild-type genes. |
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| Description | Based on the cloned cDNA, there appears to be two possible scenarios for formation of fusion genes. In some cases, the translocation apparently breaks within PAX3 intron 6 and NCOA1 intron 12 (type 1), and in other cases the translocation breaks within PAX3 intron 7 and NCOA1 intron 11 (type 2). |
| Transcript | The type 1 fusion transcript consists of the first six PAX3 exons fused to the last nine NCOA1 exons (from exon 13 onward) and the type 2 fusion transcript consists of the first seven PAX3 exons fused to the last ten NCOA1 exons (from exon 12 onward). |
| Fusion Protein |
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| Description | Comparison of wild-type and fusion products associated with the 2;2 translocation in ARMS. Conserved domains are indicated as open boxes, and functional domains are shown as solid bars. The vertical dash line indicates the translocation fusion points in the type 1 (black) and type 2 (red) fusions. Abbreviations: PB, paired box; HD, homeodomain; bHLH/PAS, basic helix-loop-helix/Per/ARNT/Sim homologous domain; LXXLL, typical LXXLL alpha-helix motifs; HAT, histone acetyltransferase (NCOA1 map adapted from Xu & Li, 2003). |
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| Description | The type 1 fusion gene encodes a 894 amino acid fusion protein and the type 2 fusion gene encodes a 1026 amino acid fusion protein. The fusion proteins encode novel transcription factors with the PAX3 DNA binding domain and the NCOA1 transcriptional activation domains. |
| Oncogenesis | Transcription dysregulation. At the cellular level there is evidence of alterations in control of growth, resulting in transformation of recipient cells (NIH3T3) in culture. |
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| Gene fusions involving PAX and FOX family members in alveolar rhabdomyosarcoma. |
| Barr FG. |
| Oncogene. 2001 Sep 10;20(40):5736-46. (REVIEW) |
| PMID 11607823 |
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| The role of Pax genes in the development of tissues and organs: Pax3 and Pax7 regulate muscle progenitor cell functions. |
| Buckingham M, Relaix F. |
| Annu Rev Cell Dev Biol. 2007;23:645-73. (REVIEW) |
| PMID 17506689 |
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| Fusions involving PAX and FOX genes in the molecular pathogenesis of alveolar rhabdomyosarcoma: recent advances. |
| Mercado GE, Barr FG. |
| Curr Mol Med. 2007 Feb;7(1):47-61. (REVIEW) |
| PMID 17311532 |
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| Use of a novel FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma. |
| Nishio J, Althof PA, Bailey JM, Zhou M, Neff JR, Barr FG, Parham DM, Teot L, Qualman SJ, Bridge JA. |
| Lab Invest. 2006 Jun;86(6):547-56. |
| PMID 16607381 |
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| Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family. |
| Sumegi J, Streblow R, Frayer RW, Dal Cin P, Rosenberg A, Meloni-Ehrig A, Bridge JA. |
| Genes Chromosomes Cancer. 2010 Mar;49(3):224-36. |
| PMID 19953635 |
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| Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1. |
| Wachtel M, Dettling M, Koscielniak E, Stegmaier S, Treuner J, Simon-Klingenstein K, Buhlmann P, Niggli FK, Schafer BW. |
| Cancer Res. 2004 Aug 15;64(16):5539-45. |
| PMID 15313887 |
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| Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. |
| Williamson D, Missiaglia E, de Reynies A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Lae M, Freneaux P, Pritchard-Jones K, Oberlin O, Shipley J, Delattre O. |
| J Clin Oncol. 2010 May 1;28(13):2151-8. Epub 2010 Mar 29. |
| PMID 20351326 |
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| Review of the in vivo functions of the p160 steroid receptor coactivator family. |
| Xu J, Li Q. |
| Mol Endocrinol. 2003 Sep;17(9):1681-92. Epub 2003 Jun 12. (REVIEW) |
| PMID 12805412 |
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| Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. |
| Xu J, Wu RC, O'Malley BW. |
| Nat Rev Cancer. 2009 Sep;9(9):615-30. (REVIEW) |
| PMID 19701241 |
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