FOXO1A gene is associated with which tumor?

• A. Embryonal rhabdomyosarcoma
• B. Synovial sarcoma
• C. Alveolar rhabdomyosarcoma
• D. Ewing sarcoma

Answer: (C)

FOXO1A’s role here is as part of the defining gene fusions in alveolar rhabdomyosarcoma. In this subtype, FOXO1A joins with PAX3 or PAX7 due to chromosomal translocations, creating PAX3-FOXO1 or PAX7-FOXO1 fusion proteins that act as powerful transcription factors driving the alveolar tumor biology. This fusion is a diagnostic hallmark that helps distinguish alveolar rhabdomyosarcoma from embryonal rhabdomyosarcoma and from other small round cell tumors. Detection by FISH or RT-PCR for these fusions supports the diagnosis. The other tumors have different, characteristic translocations (for example, synovial sarcoma with SYT-SSX and Ewing sarcoma with EWSR1-FLI1), not involving FOXO1A.