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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 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Article |
| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c745-31fe57871073d9d072b643a3a21be42005bf5243c381bcc8978921400634d9333 |
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| cites | cdi_FETCH-LOGICAL-c745-31fe57871073d9d072b643a3a21be42005bf5243c381bcc8978921400634d9333 |
| container_end_page | 117 |
| container_issue | 1 |
| container_start_page | 105 |
| container_title | Liver international |
| container_volume | 33 |
| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1111/liv.12005 |
| format | article |
| fullrecord | <record><control><sourceid>crossref</sourceid><recordid>TN_cdi_crossref_primary_10_1111_liv_12005</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>10_1111_liv_12005</sourcerecordid><originalsourceid>FETCH-LOGICAL-c745-31fe57871073d9d072b643a3a21be42005bf5243c381bcc8978921400634d9333</originalsourceid><addsrcrecordid>eNo9kMFKw0AURQdRsFYX_sHbukg7b96kkyxrsbVQFWzBZZhMJm0kTcpMIrjzE_xGv8SpinfzLrzLhXsYu0Y-wqBxXb2NUHAen7ABSpVEJAhP_72gc3bh_SvnmKYxDth2WnfW6a5qGw9tCd3OwvplCWNYP87B7Fy7D88GnN23ha3rqtmC7_O-qbqvj0-4fV4Agm6K4B4g5Hb2oLvWhGRfawdGO1M1oeOSnZW69vbq7w7ZZn63md1Hq6fFcjZdRUbJOCIsbawShVxRkRZciXwiSZMWmFt5nJWXsZBkKMHcmCRVSSpQcj4hWaRENGQ3v7XGtd47W2YHV-21e8-QZ0dAWQCU_QCib7hDV5k</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Alterations of the SWI / SNF chromatin remodelling subunit‐ BRG 1 and BRM in hepatocellular carcinoma</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>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</creator><creatorcontrib>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</creatorcontrib><description>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.</description><identifier>ISSN: 1478-3223</identifier><identifier>EISSN: 1478-3231</identifier><identifier>DOI: 10.1111/liv.12005</identifier><language>eng</language><ispartof>Liver international, 2013-01, Vol.33 (1), p.105-117</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c745-31fe57871073d9d072b643a3a21be42005bf5243c381bcc8978921400634d9333</citedby><cites>FETCH-LOGICAL-c745-31fe57871073d9d072b643a3a21be42005bf5243c381bcc8978921400634d9333</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids></links><search><creatorcontrib>Endo, Mio</creatorcontrib><creatorcontrib>Yasui, Kohichiroh</creatorcontrib><creatorcontrib>Zen, Yoh</creatorcontrib><creatorcontrib>Gen, Yasuyuki</creatorcontrib><creatorcontrib>Zen, Keika</creatorcontrib><creatorcontrib>Tsuji, Kazuhiro</creatorcontrib><creatorcontrib>Dohi, Osamu</creatorcontrib><creatorcontrib>Mitsuyoshi, Hironori</creatorcontrib><creatorcontrib>Tanaka, Shinji</creatorcontrib><creatorcontrib>Taniwaki, Masafumi</creatorcontrib><creatorcontrib>Nakanuma, Yasuni</creatorcontrib><creatorcontrib>Arii, Shigeki</creatorcontrib><creatorcontrib>Yoshikawa, Toshikazu</creatorcontrib><title>Alterations of the SWI / SNF chromatin remodelling subunit‐ BRG 1 and BRM in hepatocellular carcinoma</title><title>Liver international</title><description>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.</description><issn>1478-3223</issn><issn>1478-3231</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNo9kMFKw0AURQdRsFYX_sHbukg7b96kkyxrsbVQFWzBZZhMJm0kTcpMIrjzE_xGv8SpinfzLrzLhXsYu0Y-wqBxXb2NUHAen7ABSpVEJAhP_72gc3bh_SvnmKYxDth2WnfW6a5qGw9tCd3OwvplCWNYP87B7Fy7D88GnN23ha3rqtmC7_O-qbqvj0-4fV4Agm6K4B4g5Hb2oLvWhGRfawdGO1M1oeOSnZW69vbq7w7ZZn63md1Hq6fFcjZdRUbJOCIsbawShVxRkRZciXwiSZMWmFt5nJWXsZBkKMHcmCRVSSpQcj4hWaRENGQ3v7XGtd47W2YHV-21e8-QZ0dAWQCU_QCib7hDV5k</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>Endo, Mio</creator><creator>Yasui, Kohichiroh</creator><creator>Zen, Yoh</creator><creator>Gen, Yasuyuki</creator><creator>Zen, Keika</creator><creator>Tsuji, Kazuhiro</creator><creator>Dohi, Osamu</creator><creator>Mitsuyoshi, Hironori</creator><creator>Tanaka, Shinji</creator><creator>Taniwaki, Masafumi</creator><creator>Nakanuma, Yasuni</creator><creator>Arii, Shigeki</creator><creator>Yoshikawa, Toshikazu</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201301</creationdate><title>Alterations of the SWI / SNF chromatin remodelling subunit‐ BRG 1 and BRM in hepatocellular carcinoma</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c745-31fe57871073d9d072b643a3a21be42005bf5243c381bcc8978921400634d9333</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Endo, Mio</creatorcontrib><creatorcontrib>Yasui, Kohichiroh</creatorcontrib><creatorcontrib>Zen, Yoh</creatorcontrib><creatorcontrib>Gen, Yasuyuki</creatorcontrib><creatorcontrib>Zen, Keika</creatorcontrib><creatorcontrib>Tsuji, Kazuhiro</creatorcontrib><creatorcontrib>Dohi, Osamu</creatorcontrib><creatorcontrib>Mitsuyoshi, Hironori</creatorcontrib><creatorcontrib>Tanaka, Shinji</creatorcontrib><creatorcontrib>Taniwaki, Masafumi</creatorcontrib><creatorcontrib>Nakanuma, Yasuni</creatorcontrib><creatorcontrib>Arii, Shigeki</creatorcontrib><creatorcontrib>Yoshikawa, Toshikazu</creatorcontrib><collection>CrossRef</collection><jtitle>Liver international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Endo, Mio</au><au>Yasui, Kohichiroh</au><au>Zen, Yoh</au><au>Gen, Yasuyuki</au><au>Zen, Keika</au><au>Tsuji, Kazuhiro</au><au>Dohi, Osamu</au><au>Mitsuyoshi, Hironori</au><au>Tanaka, Shinji</au><au>Taniwaki, Masafumi</au><au>Nakanuma, Yasuni</au><au>Arii, Shigeki</au><au>Yoshikawa, Toshikazu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alterations of the SWI / SNF chromatin remodelling subunit‐ BRG 1 and BRM in hepatocellular carcinoma</atitle><jtitle>Liver international</jtitle><date>2013-01</date><risdate>2013</risdate><volume>33</volume><issue>1</issue><spage>105</spage><epage>117</epage><pages>105-117</pages><issn>1478-3223</issn><eissn>1478-3231</eissn><abstract>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.</abstract><doi>10.1111/liv.12005</doi><tpages>13</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1478-3223 |
| ispartof | Liver international, 2013-01, Vol.33 (1), p.105-117 |
| issn | 1478-3223 1478-3231 |
| language | eng |
| recordid | cdi_crossref_primary_10_1111_liv_12005 |
| source | Wiley-Blackwell Read & Publish Collection |
| title | Alterations of the SWI / SNF chromatin remodelling subunit‐ BRG 1 and BRM in hepatocellular carcinoma |
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