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Frequent co‐inactivation of the SWI/SNF subunits SMARCB1, SMARCA2 and PBRM1 in malignant rhabdoid tumours
Author(s) -
Rao Qiu,
Xia Qiuyuan,
Wang Ziyu,
Li Li,
Shen Qin,
Shi Shanshan,
Wang Xuan,
Liu Biao,
Wang Yanfen,
Shi Qunli,
Ma Henghui,
Lu Zhenfeng,
He Yan,
Zhang Rusong,
Yu Bo,
Zhou Xiaojun
Publication year - 2015
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12632
Subject(s) - smarcb1 , smarca4 , swi/snf , biology , frameshift mutation , fluorescence in situ hybridization , carcinogenesis , missense mutation , genetics , arid1a , chromosome 17 (human) , microbiology and biotechnology , cancer research , mutation , chromosome , chromatin remodeling , gene , chromatin
Aims Malignant rhabdoid tumours ( MRT s) are highly aggressive malignancies of early infancy characterized by inactivation of SMARCB 1, 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 MRT s. Methods and results We screened the key subunits of the SWI / SNF complex, including SMARCB 1, SMARCA 2, PBRM 1, SMARCA 4, and ARID 1A, in four MRT s by immunohistochemistry, sequencing, and fluorescence in‐situ hybridization ( FISH ). Complete loss of SMARCB 1, SMARCA 2 and PBRM 1 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 SMARCB 1 in one case, and monoploidy of chromosome 22, which harbours SMARCB 1 , in another case. Furthermore, trisomy of chromosome 9, which harbours SMARCA 2 , was observed in two cases. Abnormality of PBRM 1 was not found in any case. Conclusions We report, for the first time, co‐inactivation and frequent mutations of SMARCB 1 , SMARCA 2 and PBRM 1 in MRT s. Multiple subunit abnormalities of the SWI / SNF complex potentially act together to contribute to the tumorigenesis of MRT s, which provides unique insights into this disease.