Ewing sarcoma
Ewing sarcoma
复制标题
DOI：
10.1038/s41572-018-0003-x
复制
发表时间：
2018-07-05
影响因子：
81.5
通讯作者：
Dirksen, Uta
中科院分区：
文献类型：
--
作者：
Gruenewald, Thomas G. P.;Cidre-Aranaz, Florencia;Dirksen, Uta
尤文肉瘤是儿童和青少年时期第二常见的骨肿瘤，也可能出现在软组织中。尤文肉瘤是一种高度侵袭性的癌症，患有标准风险和局部疾病的患者的生存率为 70-80%，而患有转移性疾病的患者的生存率为 30%。治疗包括局部手术、放疗和联合化疗，这些疗法与急性和慢性不良反应有关，可能会损害幸存者的生活质量。在组织学上，尤文肉瘤由表达高水平 CD99 的小圆形细胞组成。从遗传学上来说，它们的特征是平衡染色体易位，其中 FET 基因家族的成员与 ETS 转录因子融合，最常见的融合是 EWSR1-FLI1（85% 的病例）。尤文肉瘤断点区域 1 蛋白 (EWSR1)-Friend 白血病整合 1 转录因子 (FLI 1) 是一种肿瘤特异性嵌合转录因子 (EWSR1-FLI1)，具有可大规模重新连接转录组的新形态效应。此外，EWSR1-FLI1 通过在 GGAA 微卫星上诱导从头增强子并改变基因调控元件的状态来重新编程表观基因组，从而创建独特的表观遗传特征。诊断时额外的突变很少见，主要涉及 STAG2、TP53 和 CDKN2A 缺失。关于尤文肉瘤分子机制的新兴研究有望改善早期检测、疾病监测、降低治疗相关毒性、总体生存率和生活质量。
Ewing sarcoma is the second most frequent bone tumour of childhood and adolescence that can also arise in soft tissue. Ewing sarcoma is a highly aggressive cancer, with a survival of 70-80% for patients with standard-risk and localized disease and similar to 30% for those with metastatic disease. Treatment comprises local surgery, radiotherapy and polychemotherapy, which are associated with acute and chronic adverse effects that may compromise quality of life in survivors. Histologically, Ewing sarcomas are composed of small round cells expressing high levels of CD99. Genetically, they are characterized by balanced chromosomal translocations in which a member of the FET gene family is fused with an ETS transcription factor, with the most common fusion being EWSR1-FLI1 (85% of cases). Ewing sarcoma breakpoint region 1 protein (EWSR1)-Friend leukaemia integration 1 transcription factor (FLI 1) is a tumour-specific chimeric transcription factor (EWSR1-FLI1) with neomorphic effects that massively rewires the transcriptome. Additionally, EWSR1-FLI1 reprogrammes the epigenome by inducing de novo enhancers at GGAA microsatellites and by altering the state of gene regulatory elements, creating a unique epigenetic signature. Additional mutations at diagnosis are rare and mainly involve STAG2, TP53 and CDKN2A deletions. Emerging studies on the molecular mechanisms of Ewing sarcoma hold promise for improvements in early detection, disease monitoring, lower treatment-related toxicity, overall survival and quality of life.