Department of Pathology, University of Utah and ARUP Laboratories, Salt Lake City, UT, USA.
Department of Pathology, Kansai Medical University, Osaka, Japan.
Semin Diagn Pathol. 2021 May;38(3):212-221. doi: 10.1053/j.semdp.2021.03.007. Epub 2021 Apr 3.
Since the discovery of association of SMARCB1 mutations with malignant rhabdoid tumors and renal medullary carcinoma, mutations in genes of the SWI/SNF chromatin remodeling complex have been increasingly identified across a diverse spectrum of neoplasms. As a group, SWI/SNF complex subunit mutations are now recognized to be the second most frequent type of mutations across tumors. SMARCB1 mutations were originally reported in malignant rhabdoid tumors of the kidney and thought to be pathognomonic for this tumor. However, more broadly, recognition of typical rhabdoid cytomorphology and SMARCB1 mutations beyond rhabdoid tumors has changed our understanding of the pathobiology of these tumors. While mutations of SWI/SNF complex are diagnostic of rhabdoid tumors and renal medullary carcinoma, their clinical relevance extends to potential prognostic and predictive utility in other tumors as well. Beyond SMARCB1, the PBRM1 and ARID1A genes are the most frequently altered members of the SWI/SNF complex in genitourinary neoplasms, especially in clear cell renal cell carcinoma and urothelial carcinoma. In this review, we provide an overview of alterations in the SWI/SNF complex encountered in genitourinary neoplasms and discuss their increasing clinical importance.
自发现 SMARCB1 突变与恶性横纹肌样肿瘤和肾髓质癌相关以来，SWI/SNF 染色质重塑复合物基因的突变已在多种肿瘤中被越来越多地发现。作为一个整体，SWI/SNF 复合物亚基突变现在被认为是肿瘤中第二常见的突变类型。SMARCB1 突变最初在肾恶性横纹肌样肿瘤中报道，被认为是该肿瘤的特征性改变。然而，更广泛地说，在横纹肌样肿瘤之外认识到典型的横纹肌样细胞形态学和 SMARCB1 突变改变了我们对这些肿瘤的病理生物学的理解。虽然 SWI/SNF 复合物的突变是横纹肌样肿瘤和肾髓质癌的诊断标志，但它们的临床意义在其他肿瘤中也扩展到潜在的预后和预测用途。除了 SMARCB1 之外，PBRM1 和 ARID1A 基因是泌尿生殖系统肿瘤中 SWI/SNF 复合物最常改变的成员，尤其是在肾透明细胞癌和尿路上皮癌中。在这篇综述中，我们概述了泌尿生殖系统肿瘤中遇到的 SWI/SNF 复合物的改变，并讨论了它们日益增加的临床重要性。
