title: Frequent co-inactivation of the SWI/SNF subunits SMARCB1, SMARCA2 and PBRM1 in malignant rhabdoid tumours.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Rao
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qiu-yuan
authors.initials: QY
authors.lastname: Xia
authors.affiliation: School of Basic Medical Sciences, Nanjing University of Traditional Chinese Medicine, Nanjing, China.
authors.forename: Zi-yu
authors.initials: ZY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Shi
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yan-fen
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qun-li
authors.initials: QL
authors.lastname: Shi
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Heng-hui
authors.initials: HH
authors.lastname: Ma
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Zhen-feng
authors.initials: ZF
authors.lastname: Lu
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Ru-song
authors.initials: RS
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Zhou
mesh_terms: D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018335:Rhabdoid Tumor / Q000235:genetics*; D000071796:SMARCB1 Protein; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors
keywords: BAF180/PBRM1; BRM/SMARCA2; INI1/SMARCB1; SWI/SNF complex; malignant rhabdoid tumour