Department of Oncohematology, IRCCS, Ospedale Pediatrico Bambino Gesù, Roma, Italy.
BMC Med. 2011 May 25;9:63. doi: 10.1186/1741-7015-9-63.
Soft tissue sarcomas of childhood are a group of heterogeneous tumors thought to be derived from mesenchymal stem cells. Surgical resection is effective only in about 50% of cases and resistance to conventional chemotherapy is often responsible for treatment failure. Therefore, investigations on novel therapeutic targets are of fundamental importance. Deregulation of epigenetic mechanisms underlying chromatin modifications during stem cell differentiation has been suggested to contribute to soft tissue sarcoma pathogenesis. One of the main elements in this scenario is enhancer of zeste homolog 2 (EZH2), a methyltransferase belonging to the Polycomb group proteins. EZH2 catalyzes histone H3 methylation on gene promoters, thus repressing genes that induce stem cell differentiation to maintain an embryonic stem cell signature. EZH2 deregulated expression/function in soft tissue sarcomas has been recently reported. In this review, an overview of the recently reported functions of EZH2 in soft tissue sarcomas is given and the hypothesis that its expression might be involved in soft tissue sarcomagenesis is discussed. Finally, the therapeutic potential of epigenetic therapies modulating EZH2-mediated gene repression is considered.
儿童软组织肉瘤是一组异质性肿瘤，被认为来源于间充质干细胞。手术切除仅在约 50%的病例中有效，对常规化疗的耐药性常常是导致治疗失败的原因。因此，对新的治疗靶点的研究至关重要。有研究表明，在干细胞分化过程中染色质修饰的表观遗传机制失调可能导致软组织肉瘤的发病机制。在这种情况下的主要因素之一是增强子结合锌指蛋白 2（EZH2），它是一种属于 Polycomb 组蛋白的甲基转移酶。EZH2 在基因启动子上催化组蛋白 H3 的甲基化，从而抑制诱导干细胞分化的基因，以维持胚胎干细胞的特征。最近有报道称，EZH2 在软组织肉瘤中的表达失调/功能失调。本文综述了 EZH2 在软组织肉瘤中的最新报道功能，并讨论了其表达可能参与软组织肉瘤发生的假说。最后，考虑了调节 EZH2 介导的基因抑制的表观遗传治疗的治疗潜力。
