Biegel Jaclyn A, Busse Tracy M, Weissman Bernard E
Am J Med Genet C Semin Med Genet. 2014 Sep;166C(3):350-66. doi: 10.1002/ajmg.c.31410. Epub 2014 Aug 28.
The identification of mutations and deletions in the SMARCB1 locus in chromosome band 22q11.2 in pediatric rhabdoid tumors provided the first evidence for the involvement of the SWI/SNF chromatin remodeling complex in cancer. Over the last 15 years, alterations in more than 20 members of the complex have been reported in a variety of human tumors. These include germline mutations and copy number alterations in SMARCB1, SMARCA4, SMARCE1, and PBRM1 that predispose carriers to both benign and malignant neoplasms. Somatic mutations, structural abnormalities, or epigenetic modifications that lead to reduced or aberrant expression of complex members have now been reported in more than 20% of malignancies, including both solid tumors and hematologic disorders in both children and adults. In this review, we will highlight the role of SMARCB1 in cancer as a paradigm for other tumors with alterations in SWI/SNF complex members and demonstrate the broad spectrum of mutations observed in complex members in different tumor types.
小儿横纹肌肉瘤中22q11.2染色体带SMARCB1基因座突变和缺失的鉴定，为SWI/SNF染色质重塑复合体参与癌症提供了首个证据。在过去15年里，该复合体20多个成员的改变已在多种人类肿瘤中被报道。这些改变包括SMARCB1、SMARCA4、SMARCE1和PBRM1的种系突变及拷贝数改变，使携带者易患良性和恶性肿瘤。目前已有报道称，超过20%的恶性肿瘤（包括儿童和成人的实体瘤及血液系统疾病）存在导致复合体成员表达降低或异常的体细胞突变、结构异常或表观遗传修饰。在本综述中，我们将重点介绍SMARCB1在癌症中的作用，以此作为SWI/SNF复合体成员发生改变的其他肿瘤的范例，并展示在不同肿瘤类型的复合体成员中观察到的广泛突变谱。
