A novel EWSR1-VGLL1 gene fusion in a soft tissue malignant myoepithelial tumor

Soft tissue myoepithelial tumors are very rare mesenchymal tumors that are currently categorized as miscellaneous neoplasms with uncertain differentiation. Although the molecular pathogenesis of soft tissue myoepithelial tumors remains unclear, EWSR1 gene fusions with a variety of partner genes are regarded as one of the major pathogenic driver events in these tumors. We herein present a case of a deep soft tissue malignant myoepithelial tumor arising in the thigh with multiple pulmonary metastases. This tumor displayed diverse and unique histological features, namely, an epithelioid glandular growth pattern, pseudorosette-like formation, and a diffuse nest and cord-like pattern within an abundant myxoid matrix. Next-generation RNA sequencing identified a novel fusion transcript, in which the in-frame junctional reads contained exon 9 of EWSR1 and exon 2 of VGLL1, resulting in the formation of a putative chimeric protein with the N-terminal transcriptional activation domain of EWSR1 and C-terminal full length of the VGLL1 protein. EWSR1-VGLL1 fusion has not been described in neoplasm before. Further molecular and functional experiments on the present EWSR1-VGLL1 fusion gene are required to elucidate its tumorigenic effect.