Alterations of the SWI / SNF chromatin remodelling subunit‐ BRG 1 and BRM in hepatocellular carcinoma

Abstract Background The SWI / SNF chromatin remodelling complex, which contains either brahma‐related gene‐1 ( BRG 1) or brahma ( BRM ) as the catalytic ATP ase, functions as a master regulator of gene expression. Aims To examine alterations of BRG 1 and BRM in hepatocellular carcinoma ( HCC ). Meth...

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Published in:Liver international 2013-01, Vol.33 (1), p.105-117
Main Authors: Endo, Mio, Yasui, Kohichiroh, Zen, Yoh, Gen, Yasuyuki, Zen, Keika, Tsuji, Kazuhiro, Dohi, Osamu, Mitsuyoshi, Hironori, Tanaka, Shinji, Taniwaki, Masafumi, Nakanuma, Yasuni, Arii, Shigeki, Yoshikawa, Toshikazu
Format: Article
Language:English
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Summary:Abstract Background The SWI / SNF chromatin remodelling complex, which contains either brahma‐related gene‐1 ( BRG 1) or brahma ( BRM ) as the catalytic ATP ase, functions as a master regulator of gene expression. Aims To examine alterations of BRG 1 and BRM in hepatocellular carcinoma ( HCC ). Methods We investigated DNA copy number aberrations in human HCC cell lines using a high‐density oligonucleotide microarray. We determined DNA copy numbers and expression levels of BRG 1 and BRM genes in primary HCC tumours, and conducted further searches for mutations in BRG 1 and BRM genes. Results Homozygous deletion of the BRG 1 gene was found in HCC cell line SNU 398. Copy number losses of BRG 1 and BRM genes were observed in 14 (26%) and 7 (13%) of 54 primary HCC tumours respectively. We found four somatic missense mutations in the BRG 1 gene in two of 36 primary HCC tumours, but no mutations in BRM gene. Expression of BRM m RNA , but not BRG 1 m RNA , was significantly reduced in primary HCC tumours, compared to non‐tumour tissue counterparts. Immunohistochemical analyses of non‐tumour liver tissues showed that BRM protein was expressed in hepatocytes and bile‐duct epithelial cells, whereas BRG 1 protein was expressed in bile‐duct epithelial cells, but not in hepatocytes. BRM protein expression was lost in nine (22.5%) of 40 HCC tumours. Loss of BRM protein expression was significantly associated with poor overall survival. Conclusion Reduced expression of BRM may contribute to the carcinogenesis of HCC . Although deletions and mutations in BRG 1 gene were identified, the role of BRG 1 in HCC tumourigenesis remains unclear.
ISSN:1478-3223
1478-3231
DOI:10.1111/liv.12005