title: BRM/SMARCA2-negative clear cell renal cell carcinoma is associated with a high percentage of BRM somatic mutations, deletions and promoter methylation.
abstract: OBJECTIVE
  The aim of this study was to investigate potential molecular mechanisms associated with loss of BRM expression in poorly differentiated clear cell renal cell carcinoma (ccRCC).
  
  
  RESULTS
  Nineteen previously selected BRM-negative RCC tissues were examined by DNA sequencing, fluorescence in-situ hybridization (FISH) and methylation-specific polymerase chain reaction (PCR) of the BRM gene. BRM mutation was identified in 78.9% (15 of 19) cases, chromosome 9 monosomy or BRM deletion in 43.8% (seven of 16) and BRM promoter region cytosine-phosphate-guanine (CpG) methylation in 42.8% (six of 14). These results indicated that 89.5% (17 of 19) of the cases harboured at least one type of BRM genetic alteration, with two or more types of alteration in 47.4% (nine of 19). Such alterations were found rarely in adjacent non-neoplastic tissues and low-grade areas of composite tumours.
  
  
  CONCLUSIONS
  BRM gene mutation, chromosome 9 monosomy or BRM deletion and CpG methylation contribute collectively to the loss of BRM expression in ccRCC. This work focusing on composite tumours indicated that BRM abnormality occurred during tumour progression.
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: Department of Pathology, Linyi People's Hospital, Linyi, China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhan
authors.affiliation: Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School Nanjing City, Nanjing, China.
authors.forename: Xiang-Shan
authors.initials: XS
authors.lastname: Fan
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Sheng-Bing
authors.initials: SB
authors.lastname: Ye
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: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wei
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: 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: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Qiu
authors.identifier: http://orcid.org/0000-0002-2674-1937
authors.initials: Q
authors.lastname: Rao
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007680:Kidney Neoplasms / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C084011:SMARCA2 protein, human; D014157:Transcription Factors
keywords: BRM/SMARCA2; SWI/SNF complex; clear cell renal cell carcinoma