SWI/SNF complex-deficient soft tissue neoplasms: An update.
SWI/SNF complex-deficient soft tissue neoplasms: An update.
复制标题
DOI：
10.1053/j.semdp.2020.05.005
复制
发表时间：
2021-05
影响因子：
2.3
通讯作者：
Hornick JL
中科院分区：
文献类型：
--
作者：
Schaefer IM;Hornick JL
SWItch蔗糖非发酵性（SWI/SNF）染色质重塑复合物是一种大型多亚基蛋白质组装体，其以ATP依赖性方式协调染色质压实和基因转录的可及性。SWI/SNF复合物作为一种关键的表观遗传调节因子，协调基因表达、细胞增殖和分化，其生物学功能部分拮抗多梳抑制复合物2。哺乳动物SWI/SNF复合物由29个基因编码的15个亚基组成，其中一些在人类癌症中，在生殖系或散发性环境中反复突变。大多数SWI/SNF缺陷型肿瘤具有共同的“横纹肌样”细胞形态学。SMARCB 1（INI 1）是软组织肿瘤中最常失活的亚基。具体而言，SMARCB 1缺陷被观察为几乎所有恶性横纹肌样肿瘤以及大多数上皮样肉瘤和低分化脉络膜的遗传标志。此外，肌上皮癌（10-40%）、皮肤外粘液样软骨肉瘤（20%）、上皮样神经鞘瘤（40%）和上皮样恶性外周神经鞘瘤（70%）的亚组显示SMARCB 1缺失。编码SS 18亚基的基因参与SS 18-SSX重排，这是滑膜肉瘤的特征性疾病，并间接使SMARCB 1失活。最后，未分化的SMARCA 4缺陷型胸部肉瘤由SMARCA 4亚基失活定义，导致SMARCA 4和SMARCA 2丢失。很少，替代但生物学上等同的关键调节因子的失活可以替代典型亚基缺陷，例如SMARCA 4在SMARCB 1保留的上皮样肉瘤中的失活。本文简要介绍了SWI/SNF复合物的生物学功能及其在人类癌症中的作用，并详细介绍了典型SWI/SNF复合物缺乏的软组织肿瘤的最新进展，相关的形态学，基因组学和免疫组化结果。
The SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex is a large multi-subunit protein assembly that orchestrates chromatin compaction and accessibility for gene transcription in an ATP-dependent manner. As a key epigenetic regulator, the SWI/SNF complex coordinates gene expression, cell proliferation and differentiation, and its biologic functions, in part, antagonize the polycomb repressive complex 2. The mammalian SWI/SNF complex consists of 15 subunits encoded by 29 genes, some of which are recurrently mutated in human cancers, in the germline or sporadic setting. Most SWI/SNF-deficient tumors share common “rhabdoid” cytomorphology. SMARCB1 (INI1) is the subunit most frequently inactivated in soft tissue neoplasms. Specifically, SMARCB1 deficiency is observed as the genetic hallmark in virtually all malignant rhabdoid tumors, and most cases of epithelioid sarcoma and poorly differentiated chordoma. In addition, subsets of myoepithelial carcinoma (10–40%), extraskeletal myxoid chondrosarcoma (20%), epithelioid schwannoma (40%), and epithelioid malignant peripheral nerve sheath tumor (70%) demonstrate SMARCB1 loss. The gene encoding the SS18 subunit is involved in the SS18-SSX rearrangement, which is pathognomonic of synovial sarcoma and indirectly inactivates SMARCB1. Finally, undifferentiated SMARCA4-deficient thoracic sarcomas are defined by SMARCA4 subunit inactivation, leading to SMARCA4 and SMARCA2 loss. Rarely, inactivation of alternate but biologically equivalent key regulators can substitute for canonical subunit deficiency, such as SMARCA4 inactivation in cases of SMARCB1-retained epithelioid sarcoma. This review briefly highlights SWI/SNF complex biologic functions and its roles in human cancer and provides a detailed update on recent advances in soft tissue neoplasms with canonical SWI/SNF complex deficiency, correlating morphologic, genomic, and immunohistochemical findings.
登录
查看更多内容
影响因子：
7.3
作者：
Bourdeaut, F.;Freneaux, P.;Delattre, O.
通讯作者：
Delattre, O.
影响因子：
3.5
作者：
Agaimy, Abbas;Fuchs, Florian;Haller, Florian
通讯作者：
Haller, Florian
影响因子：
2
作者：
Herpel, Esther;Rieker, Ralf J.;Agaimy, Abbas
通讯作者：
Agaimy, Abbas
影响因子：
64.8
作者：
De Raedt, Thomas;Beert, Eline;Cichowski, Karen
通讯作者：
Cichowski, Karen
影响因子：
--
作者：
Agaimy, Abbas
通讯作者：
Agaimy, Abbas