Soft Tissues: Embryonal rhabdomyosarcoma with t(4;22)(q35;q12) EWSR1/DUX4
2009-12-01 Jean-Loup Huret Affiliation1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Clinics and Pathology
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 (double homeobox 4)
Location
4q35.2
Protein description
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 (Ewing sarcoma breakpoint region 1)
Location
22q12.2
Protein description
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
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.
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).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 17984056 | 2007 | DUX4, a candidate gene of facioscapulohumeral muscular dystrophy, encodes a transcriptional activator of PITX1. | Dixit M et al |
| 19837262 | 2009 | Fusion of EWSR1 with the DUX4 facioscapulohumeral muscular dystrophy region resulting from t(4;22)(q35;q12) in a case of embryonal rhabdomyosarcoma. | Sirvent N et al |
Citation
Jean-Loup Huret
Soft Tissues: Embryonal rhabdomyosarcoma with t(4;22)(q35;q12) EWSR1/DUX4
Atlas Genet Cytogenet Oncol Haematol. 2009-12-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/6280/soft-tissues-embryonal-rhabdomyosarcoma-with-t(4
