RNA Expression Profiling in Cellular Myofibromas with SRF Fusions.

Abstract

Introduction: Cellular myofibroma with recurring SRF fusions is a recently described entity that can mimic myogenic sarcomas. The purpose of this study was to evaluate the gene expression profiling in these tumours. Method(s): A total of 7 cases of SRF-rearranged cellular myofibromas were included, along with 25 fusion negative samples as control. The TruSight RNA Fusion panel was performed, followed by FASTQ file processing using the BaseSpace application DRAGEN RNA Pipeline. This was followed by analysis using DRAGEN Differential Expression application, which runs the DESeq2 algorithm on RNA quantification files to output genes and transcripts that are differentially expressed between 2 sample groups. Result(s): The 7 cases of SRFrearranged tumours had 4 different fusion partners, including NCOA2 (3), RELA (2), NFKBIE (1), and NCOA3 (1). A total of 30 differentially expressed genes were identified with adjusted p values <0.05 for samples in the control and comparison groups. Of these, 4 were found to be expressed at significantly higher levels in SRF-rearranged tumours compared to the controls, including SRF, LPP, TEAD1, and VGLL3. Conclusion(s): The upregulation of SRF expression in cases of SRFrearranged tumours is well described, and similar findings were observed in our cases, which all had higher SRF expression levels compared to the mean of the control samples. Rearrangements involving LPP have been known in cases of lipomas and have also been reported rarely in myoepitheliomas. Although we did not identify any fusion involving LPP, we did identify and increase in RNA expression of LPP in SRF-rearranged tumours. TEA Domain Transcription Factor 1 (TEAD1) is known to play a role in suppressing expression of smooth muscle-specific genes by competing with myocardin for binding to serum response factor (SRF). Although there was increased expression of TEAD1 in our cases, most of them expressed smooth muscle markers. Thus, the role of TEAD1 in suppressing smooth muscle-specific genes may need further evaluation. VGLL3 amplification is a diagnostic hallmark of myxoinflammatory fibroblastic sarcoma, and its rearrangements have been reported in hybrid schwannoma-perineuriomas. An increased expression of both VGLL3 and SRF in our cases may indicate a close relationship between these tumours. Nuclear localisation of VGLL3 plays a role in collagen production by positive feedback loop, and this may contribute to prominent collagenous matrix in SRF-rearranged tumours. We have demonstrated the application of the data from a large RNA fusion panel to identify differentially expressed genes in SRF-rearranged cellular myofibromas.