Translocations involving the FOXO1 (forkhead box O1) gene at 13q14.1 and either the PAX3 (paired box 3) gene at 2q36.1 or the PAX7 (paired box 7) gene at 1p36.1 are seen frequently in cases of alveolar rhabdomyosarcoma1,2.
Rhabdomyosarcoma is the most common soft-tissue sarcoma seen in children and younger adults with two major histological subtypes: alveolar rhabdomyosarcoma (ARMS) and embryonal rhabdomyosarcoma (ERMS)3. FOXO1 rearrangements are recognised recurrent abnormalities seen in ARMS, but not seen in ERMS1,2.
Approximately 55% of cases of ARMS are associated with a PAX3-FOXO1 rearrangement via a t(2;13)(q36.1;q14) translocation and 22% of cases of ARMS are associated with a PAX7- FOXO1 rearrangement via a t(1;13)(p36;q14) translocation4. These translocations lead to the fusion of transcription factor FOXO1 to the transcription factors PAX3 and PAX7 located at 2q36.1 and 1p36.13 respectively2.
Studies have shown that ARMS patients with PAX-FOXO1 rearrangements have an inferior outcome compared to ERMS patients, whereas ARMS patients without PAX-FOXO1 rearrangements show similar outcomes to ERMS2,5.
A subset of patients with ARMS may show fusion gene amplification. This is most commonly associated with the presence of PAX7-FOXO1 rearrangements and has been shown to be associated with significantly improved outcome over ARMS patients with PAX-FOXO1 rearrangements without fusion gene amplification6.
This breakapart probe design allows the detection of FOXO1 rearrangements, regardless of the partner gene involved.
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- Skapek et al., Pediatr Blood Cancer. 2013 Sep;60(9):1411-7
- Duan et al., Genes Chromosomes Cancer. 2012 Jul;51(7):662-674