Urbini Milena, Astolfi Annalisa, Indio Valentina, Tarantino Giuseppe, Serravalle Salvatore, Saponara Maristella, Nannini Margherita, Gronchi Alessandro, Fiore Marco, Maestro Roberta, Brenca Monica, Dei Tos Angelo Paolo, Dagrada Gian Paolo, Negri Tiziana, Pilotti Silvana, Casali Paolo Giovanni, Biasco Guido, Pession Andrea, Stacchiotti Silvia, Pantaleo Maria Abbondanza
"Giorgio Prodi" Cancer Research Center, University of Bologna, Bologna, Italy.
Pediatric Hematology and Oncology Unit, S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Oncotarget. 2017 May 17;8(36):60036-60045. doi: 10.18632/oncotarget.17958. eCollection 2017 Sep 1.
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.
肌上皮肿瘤（MN）较为罕见，且情况不明，呈现出包括EWSR1、FUS和PLAG1重排在内的多种基因异常谱。然而，在其余的MN中，尚未描述其他融合基因，关于继发性获得性分子改变的知识仍然匮乏。因此，我们通过RNA测序对5例软组织MN进行了筛查，旨在鉴定新的融合转录本。在两例中检测到一种新的SRF-E2F1融合：一例其他融合为阴性，而另一例还显示存在FUS-KLF17。该融合通过独立技术得到验证，并且在两例中，SRF-E2F1仅在肿瘤块的一个亚克隆中被检测到。SRF-E2F1保持了编码框架，从而导致翻译出一种包含SRF的DNA结合结构域和E2F1的反式激活结构域的嵌合蛋白。此外，SRF-E2F1的异位表达表明嵌合转录本具有功能活性，并且可能影响肿瘤生长。在两例中的出现以及所涉及的两个基因的生物学相关性表明，SRF-E2F1融合可能成为一种有用的诊断工具。需要进一步的生物学研究来更好地评估其在MN生物学中的作用。
