Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma
Shumpei Ishikawa and colleagues report the identification of recurrent gain-of-function mutations in RHOA in diffuse-type gastric carcinomas. Diffuse-type gastric carcinoma (DGC) is characterized by a highly malignant phenotype with prominent infiltration and stromal induction. We performed whole-ex...
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| Veröffentlicht in: | Nature genetics 2014-06, Vol.46 (6), p.583-587 |
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| creator | Kakiuchi, Miwako Nishizawa, Takashi Ueda, Hiroki Gotoh, Kengo Tanaka, Atsushi Hayashi, Akimasa Yamamoto, Shogo Tatsuno, Kenji Katoh, Hiroto Watanabe, Yoshiaki Ichimura, Takashi Ushiku, Tetsuo Funahashi, Shinichi Tateishi, Keisuke Wada, Ikuo Shimizu, Nobuyuki Nomura, Sachiyo Koike, Kazuhiko Seto, Yasuyuki Fukayama, Masashi Aburatani, Hiroyuki Ishikawa, Shumpei |
| description | Shumpei Ishikawa and colleagues report the identification of recurrent gain-of-function mutations in
RHOA
in diffuse-type gastric carcinomas.
Diffuse-type gastric carcinoma (DGC) is characterized by a highly malignant phenotype with prominent infiltration and stromal induction. We performed whole-exome sequencing on 30 DGC cases and found recurrent
RHOA
nonsynonymous mutations. With validation sequencing of an additional 57 cases,
RHOA
mutation was observed in 25.3% (22/87) of DGCs, with mutational hotspots affecting the Tyr42, Arg5 and Gly17 residues in RHOA protein. These positions are highly conserved among RHO family members, and Tyr42 and Arg5 are located outside the guanine nucleotide–binding pocket. Several lines of functional evidence indicated that mutant RHOA works in a gain-of-function manner. Comparison of mutational profiles for the major gastric cancer subtypes showed that
RHOA
mutations occur specifically in DGCs, the majority of which were histopathologically characterized by the presence of poorly differentiated adenocarcinomas together with more differentiated components in the gastric mucosa. Our findings identify a potential therapeutic target for this poor-prognosis subtype of gastric cancer with no available molecularly targeted drugs. |
| doi_str_mv | 10.1038/ng.2984 |
| format | Article |
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RHOA
in diffuse-type gastric carcinomas.
Diffuse-type gastric carcinoma (DGC) is characterized by a highly malignant phenotype with prominent infiltration and stromal induction. We performed whole-exome sequencing on 30 DGC cases and found recurrent
RHOA
nonsynonymous mutations. With validation sequencing of an additional 57 cases,
RHOA
mutation was observed in 25.3% (22/87) of DGCs, with mutational hotspots affecting the Tyr42, Arg5 and Gly17 residues in RHOA protein. These positions are highly conserved among RHO family members, and Tyr42 and Arg5 are located outside the guanine nucleotide–binding pocket. Several lines of functional evidence indicated that mutant RHOA works in a gain-of-function manner. Comparison of mutational profiles for the major gastric cancer subtypes showed that
RHOA
mutations occur specifically in DGCs, the majority of which were histopathologically characterized by the presence of poorly differentiated adenocarcinomas together with more differentiated components in the gastric mucosa. Our findings identify a potential therapeutic target for this poor-prognosis subtype of gastric cancer with no available molecularly targeted drugs.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.2984</identifier><identifier>PMID: 24816255</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>13/89 ; 38/77 ; 45 ; 45/23 ; 692/699/1503/1504/1829 ; 692/699/67/395 ; Adenocarcinoma - genetics ; Agriculture ; Amino Acid Sequence ; Animal Genetics and Genomics ; Biomedicine ; Cancer ; Cancer Research ; Carcinoma - genetics ; Care and treatment ; Cell Differentiation ; DNA Mutational Analysis ; Gastric cancer ; Gastric Mucosa - pathology ; Gene Function ; Gene Library ; Gene mutations ; Genes ; Genetic aspects ; Genetic research ; Germ-Line Mutation ; Grants ; High-Throughput Nucleotide Sequencing ; Human Genetics ; Humans ; Identification and classification ; letter ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Oncology, Experimental ; Phenotype ; Prognosis ; Proteins ; rhoA GTP-Binding Protein - genetics ; RNA, Small Interfering - metabolism ; Science ; Sequence Homology, Amino Acid ; Stomach cancer ; Stomach Neoplasms - genetics ; Stromal Cells - metabolism ; Studies ; Tumors</subject><ispartof>Nature genetics, 2014-06, Vol.46 (6), p.583-587</ispartof><rights>Springer Nature America, Inc. 2014</rights><rights>COPYRIGHT 2014 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c576t-3f168934e9bb397990c1b30f68b86ccbd40bb692a20d0d42ddfd547791c784243</citedby><cites>FETCH-LOGICAL-c576t-3f168934e9bb397990c1b30f68b86ccbd40bb692a20d0d42ddfd547791c784243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.2984$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.2984$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24816255$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kakiuchi, Miwako</creatorcontrib><creatorcontrib>Nishizawa, Takashi</creatorcontrib><creatorcontrib>Ueda, Hiroki</creatorcontrib><creatorcontrib>Gotoh, Kengo</creatorcontrib><creatorcontrib>Tanaka, Atsushi</creatorcontrib><creatorcontrib>Hayashi, Akimasa</creatorcontrib><creatorcontrib>Yamamoto, Shogo</creatorcontrib><creatorcontrib>Tatsuno, Kenji</creatorcontrib><creatorcontrib>Katoh, Hiroto</creatorcontrib><creatorcontrib>Watanabe, Yoshiaki</creatorcontrib><creatorcontrib>Ichimura, Takashi</creatorcontrib><creatorcontrib>Ushiku, Tetsuo</creatorcontrib><creatorcontrib>Funahashi, Shinichi</creatorcontrib><creatorcontrib>Tateishi, Keisuke</creatorcontrib><creatorcontrib>Wada, Ikuo</creatorcontrib><creatorcontrib>Shimizu, Nobuyuki</creatorcontrib><creatorcontrib>Nomura, Sachiyo</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><creatorcontrib>Seto, Yasuyuki</creatorcontrib><creatorcontrib>Fukayama, Masashi</creatorcontrib><creatorcontrib>Aburatani, Hiroyuki</creatorcontrib><creatorcontrib>Ishikawa, Shumpei</creatorcontrib><title>Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Shumpei Ishikawa and colleagues report the identification of recurrent gain-of-function mutations in
RHOA
in diffuse-type gastric carcinomas.
Diffuse-type gastric carcinoma (DGC) is characterized by a highly malignant phenotype with prominent infiltration and stromal induction. We performed whole-exome sequencing on 30 DGC cases and found recurrent
RHOA
nonsynonymous mutations. With validation sequencing of an additional 57 cases,
RHOA
mutation was observed in 25.3% (22/87) of DGCs, with mutational hotspots affecting the Tyr42, Arg5 and Gly17 residues in RHOA protein. These positions are highly conserved among RHO family members, and Tyr42 and Arg5 are located outside the guanine nucleotide–binding pocket. Several lines of functional evidence indicated that mutant RHOA works in a gain-of-function manner. Comparison of mutational profiles for the major gastric cancer subtypes showed that
RHOA
mutations occur specifically in DGCs, the majority of which were histopathologically characterized by the presence of poorly differentiated adenocarcinomas together with more differentiated components in the gastric mucosa. Our findings identify a potential therapeutic target for this poor-prognosis subtype of gastric cancer with no available molecularly targeted drugs.</description><subject>13/89</subject><subject>38/77</subject><subject>45</subject><subject>45/23</subject><subject>692/699/1503/1504/1829</subject><subject>692/699/67/395</subject><subject>Adenocarcinoma - genetics</subject><subject>Agriculture</subject><subject>Amino Acid Sequence</subject><subject>Animal Genetics and Genomics</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Carcinoma - genetics</subject><subject>Care and treatment</subject><subject>Cell Differentiation</subject><subject>DNA Mutational Analysis</subject><subject>Gastric cancer</subject><subject>Gastric Mucosa - pathology</subject><subject>Gene Function</subject><subject>Gene Library</subject><subject>Gene mutations</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Germ-Line Mutation</subject><subject>Grants</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>letter</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Oncology, Experimental</subject><subject>Phenotype</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>rhoA GTP-Binding Protein - genetics</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Science</subject><subject>Sequence Homology, Amino Acid</subject><subject>Stomach cancer</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stromal Cells - metabolism</subject><subject>Studies</subject><subject>Tumors</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkttrFDEYxQdR7EXxP5ABH6wPsyaTTC6PS1FbKC6sl9eQyWVI2UnWXKD9783Qat3iQ8lDPpLfOfAdTtO8gWAFAWIf_bTqOcPPmmM4YNJBCtnzOgMCOwwQOWpOUroGAGIM2MvmqMcMkn4YjpuvW6NKjMbndpLOd8F2tniVXfDtXLJchtQG224vNuvW-VY7a0syXb7dmypJOTrVKhmV82GWr5oXVu6SeX1_nzY_Pn_6fn7RXW2-XJ6vrzo1UJI7ZCFhHGHDxxFxyjlQcETAEjYyotSoMRhHwnvZAw007rW2esCUcqgowz1Gp83Zne8-hl_FpCxml5TZ7aQ3oSQBSY2BDZw-AR0QQJAzxCv67hF6HUr0dZGFqtExCvoHapI7I5y3IUepFlOxRrQa0YGASq3-Q9WjzexU8Ma6-n4g-HAgqEw2N3mSJSVx-W37dHbz85B9f8eqGFKKxop9dLOMtwICsZRH-Eks5ank2_v1yzgb_Zf705aHKFP98pOJ_-TzyOs3bAfG2A</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Kakiuchi, Miwako</creator><creator>Nishizawa, Takashi</creator><creator>Ueda, Hiroki</creator><creator>Gotoh, Kengo</creator><creator>Tanaka, Atsushi</creator><creator>Hayashi, Akimasa</creator><creator>Yamamoto, Shogo</creator><creator>Tatsuno, Kenji</creator><creator>Katoh, Hiroto</creator><creator>Watanabe, Yoshiaki</creator><creator>Ichimura, Takashi</creator><creator>Ushiku, Tetsuo</creator><creator>Funahashi, Shinichi</creator><creator>Tateishi, Keisuke</creator><creator>Wada, Ikuo</creator><creator>Shimizu, Nobuyuki</creator><creator>Nomura, Sachiyo</creator><creator>Koike, Kazuhiko</creator><creator>Seto, Yasuyuki</creator><creator>Fukayama, Masashi</creator><creator>Aburatani, Hiroyuki</creator><creator>Ishikawa, Shumpei</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20140601</creationdate><title>Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma</title><author>Kakiuchi, Miwako ; Nishizawa, Takashi ; Ueda, Hiroki ; Gotoh, Kengo ; Tanaka, Atsushi ; Hayashi, Akimasa ; Yamamoto, Shogo ; Tatsuno, Kenji ; Katoh, Hiroto ; Watanabe, Yoshiaki ; Ichimura, Takashi ; Ushiku, Tetsuo ; Funahashi, Shinichi ; Tateishi, Keisuke ; Wada, Ikuo ; Shimizu, Nobuyuki ; Nomura, Sachiyo ; Koike, Kazuhiko ; Seto, Yasuyuki ; Fukayama, Masashi ; Aburatani, Hiroyuki ; Ishikawa, Shumpei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c576t-3f168934e9bb397990c1b30f68b86ccbd40bb692a20d0d42ddfd547791c784243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>13/89</topic><topic>38/77</topic><topic>45</topic><topic>45/23</topic><topic>692/699/1503/1504/1829</topic><topic>692/699/67/395</topic><topic>Adenocarcinoma - genetics</topic><topic>Agriculture</topic><topic>Amino Acid Sequence</topic><topic>Animal Genetics and Genomics</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Carcinoma - genetics</topic><topic>Care and treatment</topic><topic>Cell Differentiation</topic><topic>DNA Mutational Analysis</topic><topic>Gastric cancer</topic><topic>Gastric Mucosa - pathology</topic><topic>Gene Function</topic><topic>Gene Library</topic><topic>Gene mutations</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic research</topic><topic>Germ-Line Mutation</topic><topic>Grants</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>letter</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Oncology, Experimental</topic><topic>Phenotype</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>rhoA GTP-Binding Protein - genetics</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Science</topic><topic>Sequence Homology, Amino Acid</topic><topic>Stomach cancer</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stromal Cells - metabolism</topic><topic>Studies</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kakiuchi, Miwako</creatorcontrib><creatorcontrib>Nishizawa, Takashi</creatorcontrib><creatorcontrib>Ueda, Hiroki</creatorcontrib><creatorcontrib>Gotoh, Kengo</creatorcontrib><creatorcontrib>Tanaka, Atsushi</creatorcontrib><creatorcontrib>Hayashi, Akimasa</creatorcontrib><creatorcontrib>Yamamoto, Shogo</creatorcontrib><creatorcontrib>Tatsuno, Kenji</creatorcontrib><creatorcontrib>Katoh, Hiroto</creatorcontrib><creatorcontrib>Watanabe, Yoshiaki</creatorcontrib><creatorcontrib>Ichimura, Takashi</creatorcontrib><creatorcontrib>Ushiku, Tetsuo</creatorcontrib><creatorcontrib>Funahashi, Shinichi</creatorcontrib><creatorcontrib>Tateishi, Keisuke</creatorcontrib><creatorcontrib>Wada, Ikuo</creatorcontrib><creatorcontrib>Shimizu, Nobuyuki</creatorcontrib><creatorcontrib>Nomura, Sachiyo</creatorcontrib><creatorcontrib>Koike, Kazuhiko</creatorcontrib><creatorcontrib>Seto, Yasuyuki</creatorcontrib><creatorcontrib>Fukayama, Masashi</creatorcontrib><creatorcontrib>Aburatani, Hiroyuki</creatorcontrib><creatorcontrib>Ishikawa, Shumpei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kakiuchi, Miwako</au><au>Nishizawa, Takashi</au><au>Ueda, Hiroki</au><au>Gotoh, Kengo</au><au>Tanaka, Atsushi</au><au>Hayashi, Akimasa</au><au>Yamamoto, Shogo</au><au>Tatsuno, Kenji</au><au>Katoh, Hiroto</au><au>Watanabe, Yoshiaki</au><au>Ichimura, Takashi</au><au>Ushiku, Tetsuo</au><au>Funahashi, Shinichi</au><au>Tateishi, Keisuke</au><au>Wada, Ikuo</au><au>Shimizu, Nobuyuki</au><au>Nomura, Sachiyo</au><au>Koike, Kazuhiko</au><au>Seto, Yasuyuki</au><au>Fukayama, Masashi</au><au>Aburatani, Hiroyuki</au><au>Ishikawa, Shumpei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>46</volume><issue>6</issue><spage>583</spage><epage>587</epage><pages>583-587</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>Shumpei Ishikawa and colleagues report the identification of recurrent gain-of-function mutations in
RHOA
in diffuse-type gastric carcinomas.
Diffuse-type gastric carcinoma (DGC) is characterized by a highly malignant phenotype with prominent infiltration and stromal induction. We performed whole-exome sequencing on 30 DGC cases and found recurrent
RHOA
nonsynonymous mutations. With validation sequencing of an additional 57 cases,
RHOA
mutation was observed in 25.3% (22/87) of DGCs, with mutational hotspots affecting the Tyr42, Arg5 and Gly17 residues in RHOA protein. These positions are highly conserved among RHO family members, and Tyr42 and Arg5 are located outside the guanine nucleotide–binding pocket. Several lines of functional evidence indicated that mutant RHOA works in a gain-of-function manner. Comparison of mutational profiles for the major gastric cancer subtypes showed that
RHOA
mutations occur specifically in DGCs, the majority of which were histopathologically characterized by the presence of poorly differentiated adenocarcinomas together with more differentiated components in the gastric mucosa. Our findings identify a potential therapeutic target for this poor-prognosis subtype of gastric cancer with no available molecularly targeted drugs.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>24816255</pmid><doi>10.1038/ng.2984</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2014-06, Vol.46 (6), p.583-587 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1654685974 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 13/89 38/77 45 45/23 692/699/1503/1504/1829 692/699/67/395 Adenocarcinoma - genetics Agriculture Amino Acid Sequence Animal Genetics and Genomics Biomedicine Cancer Cancer Research Carcinoma - genetics Care and treatment Cell Differentiation DNA Mutational Analysis Gastric cancer Gastric Mucosa - pathology Gene Function Gene Library Gene mutations Genes Genetic aspects Genetic research Germ-Line Mutation Grants High-Throughput Nucleotide Sequencing Human Genetics Humans Identification and classification letter Models, Molecular Molecular Sequence Data Mutation Oncology, Experimental Phenotype Prognosis Proteins rhoA GTP-Binding Protein - genetics RNA, Small Interfering - metabolism Science Sequence Homology, Amino Acid Stomach cancer Stomach Neoplasms - genetics Stromal Cells - metabolism Studies Tumors |
| title | Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T15%3A09%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Recurrent%20gain-of-function%20mutations%20of%20RHOA%20in%20diffuse-type%20gastric%20carcinoma&rft.jtitle=Nature%20genetics&rft.au=Kakiuchi,%20Miwako&rft.date=2014-06-01&rft.volume=46&rft.issue=6&rft.spage=583&rft.epage=587&rft.pages=583-587&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/ng.2984&rft_dat=%3Cgale_proqu%3EA379837560%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1534088702&rft_id=info:pmid/24816255&rft_galeid=A379837560&rfr_iscdi=true |