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BRM / SMARCA 2‐negative clear cell renal cell carcinoma is associated with a high percentage of BRM somatic mutations, deletions and promoter methylation
Author(s) -
Xia QiuYuan,
Zhan XueMei,
Fan XiangShan,
Ye ShengBing,
Shi ShanShan,
Li Rui,
Wei Xue,
Wang Xuan,
Ma HengHui,
Lu ZhenFeng,
Zhou XiaoJun,
Rao Qiu
Publication year - 2017
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.13120
Subject(s) - biology , cancer research , dna methylation , methylation , cpg site , microbiology and biotechnology , fluorescence in situ hybridization , monosomy , mutation , gene , chromosome , genetics , gene expression , karyotype
Aims 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 (cc RCC ). Methods and 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 cc RCC . This work focusing on composite tumours indicated that BRM abnormality occurred during tumour progression.