Frequent co-inactivation of the SWI/SNF subunits SMARCB1, SMARCA2 and PBRM1 in malignant rhabdoid tumours
Frequent co-inactivation of the SWI/SNF subunits SMARCB1, SMARCA2 and PBRM1 in malignant rhabdoid tumours
复制标题
在恶性横纹肌样肿瘤中，SWI/SNF 亚基 SMARCB1、SMARCA2 和 PBRM1 频繁同时失活。
DOI：
10.1111/his.12632
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发表时间：
2015-07-01
期刊：
影响因子：
6.4
通讯作者：
Zhou, Xiao-jun
中科院分区：
文献类型：
--
作者：
Rao, Qiu;Xia, Qiu-yuan;Zhou, Xiao-jun
恶性横纹肌样瘤（Malignant rhabdoid tumors，MRT）是一种发生于婴儿早期的高度侵袭性恶性肿瘤，其特征是SMARCB 1失活，SMARCB 1是SWI/SNF染色质重塑复合物的核心成员。本研究的目的是探索的状态SWI/SNF复合物的多个关键亚基在MRTs.Methods和resultsWe筛选的SWI/SNF复合物的关键亚基，包括SMARCB 1，SMARCA 2，PBRM 1，SMARCA 4，和ARID 1A，在四个MRT免疫组化，测序和荧光原位杂交（FISH）。在所有病例中均观察到SMARCB 1、SMARCA 2和PBRM 1表达的完全丧失以及相同基因中的相应突变。这些突变包括7个错义突变、3个同义突变、4个移码突变和2个截短突变。FISH显示杂合性缺失SMARCB 1在一个案例中，和22号染色体，其中窝藏SMARCB 1，在另一种情况下，单倍性。此外，在两例病例中观察到9号染色体三体，其中含有SMARCA 2。PBRM 1的异常没有发现在任何case.ConclusionsWe报告，为第一次，共失活和频繁突变的SMARCB 1，SMARCA 2和PBRM 1的MRT。SWI/SNF复合物的多个亚基异常可能共同作用，促进MRT的肿瘤发生，这为这种疾病提供了独特的见解。
AimsMalignant rhabdoid tumours (MRTs) are highly aggressive malignancies of early infancy characterized by inactivation of SMARCB1, a core member of the SWI/SNF chromatin-remodelling complex. The aim of this study was to explore the status of multiple key subunits of the SWI/SNF complex in MRTs.Methods and resultsWe screened the key subunits of the SWI/SNF complex, including SMARCB1, SMARCA2, PBRM1, SMARCA4, and ARID1A, in four MRTs by immunohistochemistry, sequencing, and fluorescence in-situ hybridization (FISH). Complete loss of SMARCB1, SMARCA2 and PBRM1 expression and corresponding mutations in the same genes were observed in all cases. The mutations included seven missense, three same-sense, four frameshift and two truncating mutations. FISH revealed heterozygous deletion of SMARCB1 in one case, and monoploidy of chromosome 22, which harbours SMARCB1, in another case. Furthermore, trisomy of chromosome 9, which harbours SMARCA2, was observed in two cases. Abnormality of PBRM1 was not found in any case.ConclusionsWe report, for the first time, co-inactivation and frequent mutations of SMARCB1, SMARCA2 and PBRM1 in MRTs. Multiple subunit abnormalities of the SWI/SNF complex potentially act together to contribute to the tumorigenesis of MRTs, which provides unique insights into this disease.