Agaimy Abbas, Foulkes William D
Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital Erlangen, Germany.
Departments of Human Genetics, Medicine and Oncology, McGill University, Montreal, Quebec, Canada.
Semin Diagn Pathol. 2018 May;35(3):193-198. doi: 10.1053/j.semdp.2018.01.002. Epub 2018 Feb 1.
The SWItch Sucrose non-fermentable (SWI/SNF) complex is a highly conserved multi-subunit complex of proteins encoded by numerous genes mapped to different chromosomal regions. The complex regulates the process of chromatin remodelling and hence plays a central role in the epigenetic regulation of gene expression, cell proliferation and differentiation. During the last three decades, the SWI/SNF complex has been increasingly recognized as a central molecular event driving the initiation and/or progression of several benign and malignant neoplasms of different anatomic origin and having diverse histomorphological appearance. Atypical teratoid/rhabdoid tumors (AT/RT) and renal/extrarenal malignant rhabdoid tumors of childhood, epithelioid sarcoma and small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) represent the most commonly recognized SWI/SNF-driven neoplasms. Approximately one-third of pediatric malignant rhabdoid tumors are linked to germline SWI/SNF alterations (SMARCB1/INI1, rarely SMARCA4) resulting in occasional familial clustering of these highly aggressive malignancies (so-called rhabdoid tumor predisposition syndrome, RTPS, types 1 and 2, respectively). However, more recently, inherited SWI/SNF-deficiency has been linked to several benign syndromic tumors including a subset of familial schwannomatosis (linked to SMARCB1) and multiple meningiomas (linked to SMARCE1) as well as others. Beyond neoplasms, several congenital developmental functional disorders such as Coffin-Siris syndrome and intellectual disability are now known to be SWI/SNF-related. The latter are essentially not associated with SWI/SNF-driven neoplasms, although at least anecdotal cases have documented concurrence of both neoplastic and developmental disorders. This review summarizes the most important SWI/SNF-driven diseases with a main focus on neoplasms.
开关蔗糖非发酵（SWI/SNF）复合体是一种高度保守的多亚基蛋白质复合体，由许多定位在不同染色体区域的基因编码。该复合体调节染色质重塑过程，因此在基因表达、细胞增殖和分化的表观遗传调控中发挥核心作用。在过去三十年中，SWI/SNF复合体越来越被认为是驱动多种不同解剖起源和具有不同组织形态学表现的良性和恶性肿瘤发生和/或进展的核心分子事件。非典型畸胎样/横纹肌样瘤（AT/RT）和儿童肾/肾外恶性横纹肌样瘤、上皮样肉瘤以及卵巢高钙血症型小细胞癌（SCCOHT）是最常见的由SWI/SNF驱动的肿瘤。大约三分之一的儿童恶性横纹肌样瘤与种系SWI/SNF改变（SMARCB1/INI1，很少为SMARCA4）有关，导致这些高度侵袭性恶性肿瘤偶尔出现家族聚集（分别称为横纹肌样瘤易感综合征1型和2型，RTPS）。然而，最近，遗传性SWI/SNF缺陷与几种良性综合征性肿瘤有关，包括一部分家族性神经鞘瘤病（与SMARCB1有关）和多发性脑膜瘤（与SMARCE1有关）等。除了肿瘤，现在已知一些先天性发育功能障碍，如科芬-西里斯综合征和智力残疾与SWI/SNF相关。后者基本上与SWI/SNF驱动的肿瘤无关，尽管至少有个别病例记录了肿瘤性疾病和发育障碍的同时发生。本综述总结了最重要的由SWI/SNF驱动的疾病，主要关注肿瘤。
