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

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.

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

“…SRF regulates cytoskeleton and cell motility, as well as gene expression of immediate early genes, muscle-related genes, and adhesion-related genes (5)(6)(7)(8). SRF overexpression promotes tumor cell invasion and metastasis (9). It is associated with downregulation of E-cadherin expression and upregulation of N-cadherin expression in epithelial-mesenchymal transition (EMT) in gastric, peritoneal mesothelial, liver, and prostate cancer cells (10)(11)(12).…”

Genetic variant of SRF-rearranged myofibroma with a misleading nuclear expression of STAT6 and STAT6 involvement as 3′ fusion partner

“…Fumarate hydratase-deficient leiomyoma was excluded by immunohistochemistry in our case. SRF-fusions have been reported in other mesenchymal neoplasms, such as SRF-NCOA2 in infantile spindle cell rhabdomyosarcoma [8], SRF-FOXO1 and SRF-NCOA1 in a new distinctive subset of well-differentiated rhabdomyosarcoma [9], and SRF-E2F1 in myoepithelioma [10].…”

“…3b). In mesenchymal neoplasms, fusions of STAT6 typically occur in solitary fibrous tumors, for which NAB2-STAT6 fusions are highly specific [10,11]. In solitary fibrous tumors, over 40 types of NAB2-STAT6 fusion proteins have been reported and all the predicted NAB2-STAT6 fusion proteins retain the Cterminal portion of STAT6, which contains the domain of transactivation.…”

SRF-FOXO1 and SRF-NCOA1 Fusion Genes Delineate a Distinctive Subset of Well-differentiated Rhabdomyosarcoma

“…Other fusion genes involving SRF were identified in soft tissue tumors displaying muscle differentiation: SRF-RELA has been reported in atypical myopericytic tumors (9) and SRF-E2F1 in myoepithelial tumors (22). SRF, located on 6p21, encodes a MADS box family transcriptional factor which regulates, through binding to the CArG box motif, genes involved in cell growth, migration, cytoskeletal organization, and myogenesis (23).…”