Pathology Unit, National Cancer Institute "Fondazione G. Pascale", Via Mariano Semmola, 80131 Naples, Italy.
Med Oncol. 2013 Mar;30(1):412. doi: 10.1007/s12032-012-0412-8. Epub 2013 Jan 18.
Soft tissue tumors are a heterogeneous group of tumors, traditionally classified according to morphology and histogenesis. Molecular classification divides sarcomas into two main categories: (a) sarcomas with specific genetic alterations and (b) sarcomas showing multiple complex karyotypic abnormalities without any specific pattern. Most chromosomal alterations are represented by translocations which are increasingly detected. The identification of fusion transcripts, in fact, not only support the diagnosis but also provides the basis for the development of new therapeutic strategies aimed at blocking aberrant activity of the chimeric proteins. One of the genes most susceptible to breakage/translocation in soft tissue tumors is represented by Ewing sarcoma breakpoint region 1 (EWSR1). This gene has a large number of fusion partners, mainly associated with the pathogenesis of Ewing's sarcoma but with other soft tissue tumors too. In this review, we illustrate the characteristics of this gene/protein, both in normal cellular physiology and in carcinogenesis. We describe the different fusion partners of EWSR1, the molecular pathways in which is involved and the main molecular biology techniques for the identification of fusion transcripts and for their inhibition.
软组织肿瘤是一组异质性肿瘤，传统上根据形态学和组织发生进行分类。分子分类将肉瘤分为两大类：(a)具有特定遗传改变的肉瘤和(b)表现出多种复杂核型异常而无任何特定模式的肉瘤。大多数染色体改变由易位表示，易位越来越多地被检测到。融合转录本的鉴定不仅支持诊断，而且为开发旨在阻断嵌合蛋白异常活性的新治疗策略提供了基础。在软组织肿瘤中最易发生断裂/易位的基因之一是尤文肉瘤断点区域 1（EWSR1）。该基因有大量的融合伙伴，主要与尤文肉瘤的发病机制有关，但也与其他软组织肿瘤有关。在这篇综述中，我们说明了该基因/蛋白在正常细胞生理学和癌变中的特征。我们描述了 EWSR1 的不同融合伙伴、其涉及的分子途径以及用于鉴定融合转录本及其抑制的主要分子生物学技术。
