Abstract
BACKGROUND: Leiomyomas of the gastrointestinal tract (GI) are benign smooth muscle neoplasms with limited genetic characterization. Molecular investigations may improve diagnostic classification and enhance understanding of their biological behavior. METHODS: RNA sequencing using multiple fusion-detection algorithms was performed on an ileal leiomyoma. Key findings were validated by RT-PCR and Sanger sequencing. RESULTS: A MYH11::GLI3 fusion was identified. Additional chimeric transcripts were detected but interpreted as secondary events based on limited read support. The biological relevance of MYH11::GLI3 relates to smooth muscle specific MYH11 expression and GLI3-mediated Hedgehog signaling. CONCLUSION: This study reports, for the first time, the identification of a MYH11::GLI3 chimera in gastrointestinal leiomyoma, thereby expanding the molecular spectrum of these tumors. Deregulation of GLI3 may represent an alternative mechanism of Hedgehog pathway perturbation in this neoplasm. The frequency and clinical significance of GLI3-rearranged gastrointestinal smooth muscle tumors remain to be determined.