Download Solid Tumour Section t(4;22)(q35;q12) in embryonal rhabdomyo-sarcoma (ERMS) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Solid Tumour Section
Short Communication
t(4;22)(q35;q12) in embryonal rhabdomyo-sarcoma
(ERMS)
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
(JLH)
Published in Atlas Database: December 2009
Online updated version : http://AtlasGeneticsOncology.org/Tumors/t0422q35q12RhabdoID6280.html
DOI: 10.4267/2042/44879
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
EWSR1
Clinics and pathology
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.
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
Result of the chromosomal
anomaly
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).
Hybrid Gene
Cytogenetics
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.
Cytogenetics Morphological
The t(4;22)(q35;q12) was the sole anomaly.
Fusion Protein
Genes involved and proteins
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
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).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)
References
Dixit M, Ansseau E, Tassin A, Winokur S, Shi R, Qian H,
Sauvage S, Mattéotti C, van Acker AM, Leo O, Figlewicz D,
Barro M, Laoudj-Chenivesse D, Belayew A, Coppée F, Chen
YW. DUX4, a candidate gene of facioscapulohumeral muscular
996
t(4;22)(q35;q12) in embryonal rhabdomyosarcoma (ERMS)
Huret JL
dystrophy, encodes a transcriptional activator of PITX1. Proc
Natl Acad Sci U S A. 2007 Nov 13;104(46):18157-62
This article 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.
Sirvent N, Trassard M, Ebran N, Attias R, Pedeutour F. Fusion
of EWSR1 with the DUX4 facioscapulohumeral muscular
dystrophy region resulting from t(4;22)(q35;q12) in a case of
embryonal rhabdomyosarcoma. Cancer Genet Cytogenet.
2009 Nov;195(1):12-8
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(10)
997