| Written | 2009-12 | Jean-Loup Huret |
| Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France |
| Identity |
| ICD-Topo | C470-C476,C478-C479,C490-C496,C498-C499 CONNECTIVE & SOFT TISSUE |
| ICD-Morpho | 8910/3 Embryonal rhabdomyosarcoma |
| Atlas_Id | 6280 |
| Phylum | Soft Tissues::Rhabdomyosarcoma |
| Clinics and Pathology |
| Disease | Rhabdomyosarcomas, the most common pediatric soft tissue sarcomas, are tumours related to the skeletal muscle lineage. The 2 major subtypes are alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS). Other subtypes are botryoid, spindle cell, anaplastic, pleomorphic, and undifferentiated RMS. Most ERMS are characterized by chromosome gains and a loss of heterozygocity in 11p15. |
| Epidemiology | Only one case to date, a 19-year-old female patient with an embryonal RMS, who was alive and well 6 years after diagnosis (Sirvent et al., 2009). |
| Cytogenetics |
| Cytogenetics Morphological | The t(4;22)(q35;q12) was the sole anomaly. |
| Genes involved and Proteins |
| Gene Name | DUX4 |
| Location | 4q35 |
| Protein | DUX4 (double homeobox, chromosome 4) contains two homeodomains (about 60 amino acids, involved in DNA-binding), each similar in sequence to PAX3 and PAX7 homeodomains. It is a transcription factor DUX4 is involved in myogenic differentiation and cell-cycle control (Dixit et al., 2007). |
| Gene Name | EWSR1 |
| Location | 22q12 |
| Protein | From N-term to C-term: a transactivation domain (TAD) containing multiple degenerate hexapeptide repeats, 3 arginine/glycine rich domains (RGG regions), a RNA recognition motif, and a RanBP2 type Zinc finger. Role in transcriptional regulation for specific genes and in mRNA splicing. |
| Result of the chromosomal anomaly |
| Hybrid Gene | |
| Description | Breakpoints were located in the EWSR1 gene at 22q12 and the region of the DUX4 at 4q35. A 5' EWSR1 - 3' DUX4 hybrid gene is likely. |
| Fusion Protein | |
| Description | One may speculate that the N terminal transactivation domain of EWSR1 was fused to one of the DNA binding domains of DUX4 (either the domain amino acids 19-78, or the domain aa 94-153). |
| Bibliography |
| DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1. |
| Dixit M, Ansseau E, Tassin A, Winokur S, Shi R, Qian H, Sauvage S, Matteotti C, van Acker AM, Leo O, Figlewicz D, Barro M, Laoudj-Chenivesse D, Belayew A, Coppee F, Chen YW. |
| Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18157-62. |
| PMID 17984056 |
| Fusion of EWSR1 withthe DUX4 facioscapulohumeral muscular dystrophy region resulting from t(4;22)(q35;q12) in a case of embryonal rhabdomyosarcoma. |
| Sirvent N, Trassard M, Ebran N, Attias R, Pedeutour F. |
| Cancer Genet Cytogenet. 2009 Nov;195(1):12-8. |
| PMID 19837262 |
| Citation |
| This paper should be referenced as such : |
| Huret, JL |
| t(4;22)(q35;q12) in embryonal rhabdomyosarcoma (ERMS) |
| Atlas Genet Cytogenet Oncol Haematol. 2010;14(10):996-997. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Tumors/t0422q35q12RhabdoID6280.html |
| Other genes implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Genes | EWSR1 |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(4;22)(q35;q12) EWSR1/DUX4 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Fri Jun 30 11:25:15 CEST 2017 |
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