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.

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).

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.

FLI1 (Friend leukemia virus integration 1)

11q24.3

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.

EWSR1 (Ewing sarcoma breakpoint region 1)

22q12.2

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.

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

Fusion of the N terminal transactivation domain of EWSR1 to the ETS type DNA binding domain of FLI1.