Frequent co‐inactivation of the SWI/SNF subunits SMARCB1, SMARCA2 and PBRM1 in malignant rhabdoid tumours. Issue 1 (5th February 2015)

• Record Type: Journal Article
• Authors: Rao, Qiu; Xia, Qiu‐yuan; Wang, Zi‐yu; Li, Li; Shen, Qin; Shi, Shan‐shan; Wang, Xuan; Liu, Biao; Wang, Yan‐fen; Shi, Qun‐li; Ma, Heng‐hui; Lu, Zhen‐feng; He, Yan; Zhang, Ru‐song; Yu, Bo; Zhou, Xiao‐jun
• Is Part Of: Histopathology. Volume 67:Issue 1(2015)
• Page Start: 121
• Page End: 129
• Publication Date: 2015-02-05
• Subjects: Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12632
• Languages: English
• ISSNs: 0309-0167

Abstract

<abstract abstract-type="main" id="his12632-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="his12632-sec-0001" sec-type="section"> <title>Aims</title> <p>Malignant 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.</p> </sec> <sec id="his12632-sec-0002" sec-type="section"> <title>Methods and results</title> <p>We screened the key subunits of the SWI/SNF complex, including SMARCB1, SMARCA2, PBRM1, SMARCA4, and ARID1A, in four MRTs by immunohistochemistry, sequencing, and fluorescence <italic>in‐situ</italic> 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 <italic>SMARCB1</italic> in one case, and monoploidy of chromosome 22, which harbours <italic>SMARCB1</italic>, in another case. Furthermore, trisomy of chromosome 9, which harbours <italic>SMARCA2</italic>, was observed in two cases. Abnormality of <italic>PBRM1</italic> was not found in any case.</p> </sec> <sec id="his12632-sec-0003" sec-type="section"> <title>Conclusions</title> <p>We report, for the first time, co‐inactivation and frequent mutations of <italic>SMARCB1</italic>, <italic> SMARCA2</italic> and <italic>PBRM1</italic> 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.</p> </sec> </abstract>