Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

Soft Tissues: Embryonal rhabdomyosarcoma with t(4;22)(q35;q12) EWSR1/DUX4

Written2009-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


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
WHO/OMS Classification Soft Tissues

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).


The t(4;22)(q35;q12) was the sole anomaly.

Genes involved and Proteins

Gene NameDUX4 (double homeobox 4)
Location 4q35.2
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 NameEWSR1 (Ewing sarcoma breakpoint region 1)
Location 22q12.2
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).


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


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 :

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

Mitelman database t(4;22)(q35;q12) [Fusion]     t(4;22)(q35;q12) [Cytogenetics Case]
COSMIC[ EWSR1 ]   [ DUX4 ]
Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us