Identification of SRF-E2F1 fusion transcript in EWSR-negative myoepithelioma of the soft tissue

// Milena Urbini 1 , Annalisa Astolfi 1 , Valentina Indio 1 , Giuseppe Tarantino 1 , Salvatore Serravalle 2 , Maristella Saponara 3 , Margherita Nannini 3 , Alessandro Gronchi 4 , Marco Fiore 4 , Roberta Maestro 5 , Monica Brenca 5 , Angelo Paolo Dei Tos 6 , Gian Paolo Dagrada 7 , Tiziana Negri 7 , Silvana Pilotti 7 , Paolo Giovanni Casali 8 , Guido Biasco 1 , Andrea Pession 1,2 , Silvia Stacchiotti 8 and Maria Abbondanza Pantaleo 1,3 1 “Giorgio Prodi” Cancer Research Center, University of Bologna, Bologna, Italy 2 Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy 3 Department of Specialized, Experimental and Diagnostic Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy 4 Department of Surgery, Melanoma and Sarcoma Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 5 Unit of Experimental Oncology 1, CRO Aviano National Cancer Institute, Aviano, Italy 6 Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy 7 Department of Diagnostic Pathology and Laboratory, Laboratory of Experimental Molecular Pathology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy 8 Cancer Medicine Department, Adult Mesenchymal Tumour and Rare Cancer Medical Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy Correspondence to: Maristella Saponara, email: // Keywords : myoepithelial neoplasm; SRF; E2F1; fusion; sarcoma Received : April 05, 2017 Accepted : May 01, 2017 Published : May 17, 2017 Abstract Myoepithelial neoplasms (MN) are rare and not well-circumstanced entities displaying a heterogeneous spectrum of genetic abnormalities, including EWSR1, FUS and PLAG1 rearrangements. However, in the remaining MN no other fusion gene has been described and knowledge concerning secondary acquired molecular alterations is still poor. Therefore, we screened 5 cases of MN of the soft tissue by RNA sequencing with the aim of identifying novel fusion transcripts. A novel SRF-E2F1 fusion was detected in two cases: one was negative for other fusions while the other showed also the presence of FUS-KLF17. The fusion was validated through independent techniques and, in both cases, SRF-E2F1 was detected only in a subclone of the tumoral mass. SRF-E2F1 maintained the coding frame, thus leading to the translation of a chimeric protein containing the DNA-binding domain of SRF and the trans-activation domain of E2F1. Moreover, ectopical expression of SRF-E2F1 demonstrated that the chimeric transcript is functionally active and could affect tumor growth. Occurrence in two cases and biological relevance of the two genes involved suggest that the SRF-E2F1 fusion might become a helpful diagnostic tool. Further biologic studies are needed to better assess its role in MN biology.