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t(11;22)(q24;q12) in rhabdomyosarcomas (RMS)

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.
Note Most ARMS cases are characterised by either a t(2;13)(q35;q14), resulting in a PAX3/FOXO1 hybrid gene, or a t(1;13)(p36;q14) resulting in a PAX7/FOXO1 hybrid gene. Most ERMS are characterized by chromosome gains and a loss of heterozygocity in 11p15.
Epidemiology Three cases of RMS with t(11;22)(q24;q12) have been described to date, including a two-years-old girl with a mixed embryonal and alveolar RMS, who died 14 months after diagnosis, a 4.5-year-old girl, also with a mixed embryonal and alveolar RMS, who was alive and well 9 months after diagnosis (Sorensen et al., 1993; Thorner et al., 1996).

Genetics

Note A t(2;13) hybrid transcript was excluded in the two cases described by Thorner et al., 1996. In the 4.5-year-old girl case, a highly abnormal karyotype was found, with 85 to 200 chromosomes per mitosis, and MDM2 was amplified more than a hundred times.

Genes involved and Proteins

Gene Name FLI1
Location 11q24
Protein From N-term to C-term: a 5' ETS domain, a Fli-1-specific transcriptional activation domain, and a 3' ETS transcriptional activation domain. Member of ETS transcription factor gene family. FLI1 binds to DNA in a sequence-specific manner.

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 5' EWSR1 - 3' FLI1. EWSR1 exon 7 is fused in frame to FLI1 exon 6.
Fusion Protein
Description Fusion of the N terminal transactivation domain of EWSR1 to the ETS type DNA binding domain of FLI1.
  

Bibliography

Reverse transcriptase PCR amplification of EWS/FLI-1 fusion transcripts as a diagnostic test for peripheral primitive neuroectodermal tumors of childhood.
Sorensen PH, Liu XF, Delattre O, Rowland JM, Biggs CA, Thomas G, Triche TJ.
Diagn Mol Pathol. 1993 Sep;2(3):147-57.
PMID 7506981
 
Is the EWS/FLI-1 fusion transcript specific for Ewing sarcoma and peripheral primitive neuroectodermal tumor? A report of four cases showing this transcript in a wider range of tumor types.
Thorner P, Squire J, Chilton-MacNeil S, Marrano P, Bayani J, Malkin D, Greenberg M, Lorenzana A, Zielenska M.
Am J Pathol. 1996 Apr;148(4):1125-38.
PMID 8644855
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic se arch in PubMed

Contributor(s)

Written06-2010Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Citation

This paper should be referenced as such :
Huret JL . t(11;22)(q24;q12) in rhabdomyosarcomas (RMS). Atlas Genet Cytogenet Oncol Haematol. June 2010 .
URL : http://AtlasGeneticsOncology.org/Tumors/t1122q24q12RhabdoID6285.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/handle/2042/44990/06-2010-t1122q24q12RhabdoID6285.pdf   [ Bibliographic record ]

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