Soft Tissues: Rhabdomyosarcomas with t(11;22)(q24;q12) EWSR1/FLI1

2010-06-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

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 (Friend leukemia virus integration 1)

Location

11q24.3

Protein description

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 (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

5 EWSR1 - 3 FLI1. EWSR1 exon 7 is fused in frame to FLI1 exon 6.

Bibliography

Pubmed IDLast YearTitleAuthors
75069811993Reverse transcriptase PCR amplification of EWS/FLI-1 fusion transcripts as a diagnostic test for peripheral primitive neuroectodermal tumors of childhood.Sorensen PH et al
86448551996Is 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 et al

External Links

Citation

Jean-Loup Huret

Soft Tissues: Rhabdomyosarcomas with t(11;22)(q24;q12) EWSR1/FLI1

Atlas Genet Cytogenet Oncol Haematol. 2010-06-01

Online version: http://atlasgeneticsoncology.org/solid-tumor/6285/soft-tissues-rhabdomyosarcomas-with-t(11;22)(q24;q12)-ewsr1-fli1