Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3
Michael Zeschnigk and colleagues identify recurrent somatic mutations of EIF1AX and SF3B1 in uveal melanomas with disomy 3. The EIF1AX mutations specifically alter the N-terminal tail of the protein and were found exclusively in tumors lacking SF3B1 mutations. Gene expression profiles and chromosome...
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| Veröffentlicht in: | Nature genetics 2013-08, Vol.45 (8), p.933-936 |
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| creator | Martin, Marcel Maßhöfer, Lars Temming, Petra Rahmann, Sven Metz, Claudia Bornfeld, Norbert van de Nes, Johannes Klein-Hitpass, Ludger Hinnebusch, Alan G Horsthemke, Bernhard Lohmann, Dietmar R Zeschnigk, Michael |
| description | Michael Zeschnigk and colleagues identify recurrent somatic mutations of
EIF1AX
and
SF3B1
in uveal melanomas with disomy 3. The
EIF1AX
mutations specifically alter the N-terminal tail of the protein and were found exclusively in tumors lacking
SF3B1
mutations.
Gene expression profiles and chromosome 3 copy number divide uveal melanomas into two distinct classes correlating with prognosis
1
,
2
,
3
. Using exome sequencing, we identified recurrent somatic mutations in
EIF1AX
and
SF3B1
, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either
EIF1AX
(15; 48%) or
SF3B1
(9; 29%). Mutations were infrequent (2/35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis
2
. Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either
SF3B1
(7; 54%) or
EIF1AX
(1; 8%). All
EIF1AX
mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19
SF3B1
mutations encoded an alteration of Arg625. Resequencing of ten uveal melanomas with disomy 3 that developed metastases identified
SF3B1
mutations in three tumors, none of which targeted Arg625. |
| doi_str_mv | 10.1038/ng.2674 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4307600</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A341556743</galeid><sourcerecordid>A341556743</sourcerecordid><originalsourceid>FETCH-LOGICAL-c598t-fa23151b72ef2bb8b073b3310752063ac525668dd66714561717bb8f8e3e0b033</originalsourceid><addsrcrecordid>eNqNkk1v1DAQhiMEoh8g_gGyxAE47GLHseO9VFqqXVipUiUKiJvlOJPUJbGLnfTj3zNRS9utkEA-2B4_88rzzmTZK0bnjHL1wbfzXJbFk2yXiULOWMnUUzxTyWYF5XIn20vpjFJWFFQ9z3ZyXi44zeVu9nN1FXogCX6N4K3zLXE1-ME1DhKJYMcY8UpS6M3gLOnHAffgE3GerDZrtvxBjK_JyZp_ZFNsvADTkR464zGFXLrhlNQO068Jf5E9a0yX4OXtvp99W6--Hn6eHR1_2hwuj2ZWLNQwa0zOmWBVmUOTV5WqaMkrzhktRU4lN1bkQkpV11KWrBASiy0RaxRwoBXlfD87uNE9H6seaosFRNPp8-h6E691ME5vv3h3qttwoQtOS0kpCry7FYgBfUmD7l2y0GFREMakmRDFolCCL_6NFkxIirolom8eoWdhjB6dQCpX2CYl6D3Vmg60803AL9pJVC85igls81Ti_C8Urhp6Z4OHxmF8K-H9VgIyA1wNrRlT0puTL__PHn_fZt_esDaGlCI0dzYzqqfR1L7V02gi-fphV-64P7N4b2XCJ99CfODPI63fRIDmvg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1428036850</pqid></control><display><type>article</type><title>Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3</title><source>MEDLINE</source><source>Nature Journals Online</source><source>SpringerLink Journals - AutoHoldings</source><creator>Martin, Marcel ; Maßhöfer, Lars ; Temming, Petra ; Rahmann, Sven ; Metz, Claudia ; Bornfeld, Norbert ; van de Nes, Johannes ; Klein-Hitpass, Ludger ; Hinnebusch, Alan G ; Horsthemke, Bernhard ; Lohmann, Dietmar R ; Zeschnigk, Michael</creator><creatorcontrib>Martin, Marcel ; Maßhöfer, Lars ; Temming, Petra ; Rahmann, Sven ; Metz, Claudia ; Bornfeld, Norbert ; van de Nes, Johannes ; Klein-Hitpass, Ludger ; Hinnebusch, Alan G ; Horsthemke, Bernhard ; Lohmann, Dietmar R ; Zeschnigk, Michael</creatorcontrib><description>Michael Zeschnigk and colleagues identify recurrent somatic mutations of
EIF1AX
and
SF3B1
in uveal melanomas with disomy 3. The
EIF1AX
mutations specifically alter the N-terminal tail of the protein and were found exclusively in tumors lacking
SF3B1
mutations.
Gene expression profiles and chromosome 3 copy number divide uveal melanomas into two distinct classes correlating with prognosis
1
,
2
,
3
. Using exome sequencing, we identified recurrent somatic mutations in
EIF1AX
and
SF3B1
, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either
EIF1AX
(15; 48%) or
SF3B1
(9; 29%). Mutations were infrequent (2/35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis
2
. Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either
SF3B1
(7; 54%) or
EIF1AX
(1; 8%). All
EIF1AX
mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19
SF3B1
mutations encoded an alteration of Arg625. Resequencing of ten uveal melanomas with disomy 3 that developed metastases identified
SF3B1
mutations in three tumors, none of which targeted Arg625.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.2674</identifier><identifier>PMID: 23793026</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>692/699/67/1484 ; Agriculture ; Amino Acid Sequence ; Aneuploidy ; Animal Genetics and Genomics ; Biomedicine ; Cancer Research ; Chromosomes, Human, Pair 3 ; DNA Copy Number Variations ; DNA sequencing ; Eukaryotic Initiation Factor-1 - chemistry ; Eukaryotic Initiation Factor-1 - genetics ; Exome ; Female ; Gene expression ; Gene Expression Profiling ; Gene Function ; Gene mutations ; Genetic aspects ; High-Throughput Nucleotide Sequencing ; Human Genetics ; Humans ; letter ; Male ; Melanoma ; Melanoma - genetics ; Melanoma - mortality ; Melanoma - pathology ; Microsatellite Repeats ; Molecular Sequence Data ; Monosomy - genetics ; Mutation ; Neoplasm Metastasis ; Nucleotide sequencing ; Phosphoproteins - genetics ; Physiological aspects ; Prognosis ; Ribonucleoprotein, U2 Small Nuclear - genetics ; Risk factors ; RNA Splicing Factors ; Sequence Alignment ; Tumors ; Uveal Neoplasms - genetics ; Uveal Neoplasms - mortality ; Uveal Neoplasms - pathology</subject><ispartof>Nature genetics, 2013-08, Vol.45 (8), p.933-936</ispartof><rights>Springer Nature America, Inc. 2013</rights><rights>COPYRIGHT 2013 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2013</rights><rights>2013 Nature America, Inc. All rights reserved. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c598t-fa23151b72ef2bb8b073b3310752063ac525668dd66714561717bb8f8e3e0b033</citedby><cites>FETCH-LOGICAL-c598t-fa23151b72ef2bb8b073b3310752063ac525668dd66714561717bb8f8e3e0b033</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.2674$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.2674$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23793026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Martin, Marcel</creatorcontrib><creatorcontrib>Maßhöfer, Lars</creatorcontrib><creatorcontrib>Temming, Petra</creatorcontrib><creatorcontrib>Rahmann, Sven</creatorcontrib><creatorcontrib>Metz, Claudia</creatorcontrib><creatorcontrib>Bornfeld, Norbert</creatorcontrib><creatorcontrib>van de Nes, Johannes</creatorcontrib><creatorcontrib>Klein-Hitpass, Ludger</creatorcontrib><creatorcontrib>Hinnebusch, Alan G</creatorcontrib><creatorcontrib>Horsthemke, Bernhard</creatorcontrib><creatorcontrib>Lohmann, Dietmar R</creatorcontrib><creatorcontrib>Zeschnigk, Michael</creatorcontrib><title>Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Michael Zeschnigk and colleagues identify recurrent somatic mutations of
EIF1AX
and
SF3B1
in uveal melanomas with disomy 3. The
EIF1AX
mutations specifically alter the N-terminal tail of the protein and were found exclusively in tumors lacking
SF3B1
mutations.
Gene expression profiles and chromosome 3 copy number divide uveal melanomas into two distinct classes correlating with prognosis
1
,
2
,
3
. Using exome sequencing, we identified recurrent somatic mutations in
EIF1AX
and
SF3B1
, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either
EIF1AX
(15; 48%) or
SF3B1
(9; 29%). Mutations were infrequent (2/35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis
2
. Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either
SF3B1
(7; 54%) or
EIF1AX
(1; 8%). All
EIF1AX
mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19
SF3B1
mutations encoded an alteration of Arg625. Resequencing of ten uveal melanomas with disomy 3 that developed metastases identified
SF3B1
mutations in three tumors, none of which targeted Arg625.</description><subject>692/699/67/1484</subject><subject>Agriculture</subject><subject>Amino Acid Sequence</subject><subject>Aneuploidy</subject><subject>Animal Genetics and Genomics</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Chromosomes, Human, Pair 3</subject><subject>DNA Copy Number Variations</subject><subject>DNA sequencing</subject><subject>Eukaryotic Initiation Factor-1 - chemistry</subject><subject>Eukaryotic Initiation Factor-1 - genetics</subject><subject>Exome</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Function</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>letter</subject><subject>Male</subject><subject>Melanoma</subject><subject>Melanoma - genetics</subject><subject>Melanoma - mortality</subject><subject>Melanoma - pathology</subject><subject>Microsatellite Repeats</subject><subject>Molecular Sequence Data</subject><subject>Monosomy - genetics</subject><subject>Mutation</subject><subject>Neoplasm Metastasis</subject><subject>Nucleotide sequencing</subject><subject>Phosphoproteins - genetics</subject><subject>Physiological aspects</subject><subject>Prognosis</subject><subject>Ribonucleoprotein, U2 Small Nuclear - genetics</subject><subject>Risk factors</subject><subject>RNA Splicing Factors</subject><subject>Sequence Alignment</subject><subject>Tumors</subject><subject>Uveal Neoplasms - genetics</subject><subject>Uveal Neoplasms - mortality</subject><subject>Uveal Neoplasms - pathology</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkk1v1DAQhiMEoh8g_gGyxAE47GLHseO9VFqqXVipUiUKiJvlOJPUJbGLnfTj3zNRS9utkEA-2B4_88rzzmTZK0bnjHL1wbfzXJbFk2yXiULOWMnUUzxTyWYF5XIn20vpjFJWFFQ9z3ZyXi44zeVu9nN1FXogCX6N4K3zLXE1-ME1DhKJYMcY8UpS6M3gLOnHAffgE3GerDZrtvxBjK_JyZp_ZFNsvADTkR464zGFXLrhlNQO068Jf5E9a0yX4OXtvp99W6--Hn6eHR1_2hwuj2ZWLNQwa0zOmWBVmUOTV5WqaMkrzhktRU4lN1bkQkpV11KWrBASiy0RaxRwoBXlfD87uNE9H6seaosFRNPp8-h6E691ME5vv3h3qttwoQtOS0kpCry7FYgBfUmD7l2y0GFREMakmRDFolCCL_6NFkxIirolom8eoWdhjB6dQCpX2CYl6D3Vmg60803AL9pJVC85igls81Ti_C8Urhp6Z4OHxmF8K-H9VgIyA1wNrRlT0puTL__PHn_fZt_esDaGlCI0dzYzqqfR1L7V02gi-fphV-64P7N4b2XCJ99CfODPI63fRIDmvg</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>Martin, Marcel</creator><creator>Maßhöfer, Lars</creator><creator>Temming, Petra</creator><creator>Rahmann, Sven</creator><creator>Metz, Claudia</creator><creator>Bornfeld, Norbert</creator><creator>van de Nes, Johannes</creator><creator>Klein-Hitpass, Ludger</creator><creator>Hinnebusch, Alan G</creator><creator>Horsthemke, Bernhard</creator><creator>Lohmann, Dietmar R</creator><creator>Zeschnigk, Michael</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><scope>5PM</scope></search><sort><creationdate>20130801</creationdate><title>Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3</title><author>Martin, Marcel ; Maßhöfer, Lars ; Temming, Petra ; Rahmann, Sven ; Metz, Claudia ; Bornfeld, Norbert ; van de Nes, Johannes ; Klein-Hitpass, Ludger ; Hinnebusch, Alan G ; Horsthemke, Bernhard ; Lohmann, Dietmar R ; Zeschnigk, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c598t-fa23151b72ef2bb8b073b3310752063ac525668dd66714561717bb8f8e3e0b033</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>692/699/67/1484</topic><topic>Agriculture</topic><topic>Amino Acid Sequence</topic><topic>Aneuploidy</topic><topic>Animal Genetics and Genomics</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Chromosomes, Human, Pair 3</topic><topic>DNA Copy Number Variations</topic><topic>DNA sequencing</topic><topic>Eukaryotic Initiation Factor-1 - chemistry</topic><topic>Eukaryotic Initiation Factor-1 - genetics</topic><topic>Exome</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Function</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>letter</topic><topic>Male</topic><topic>Melanoma</topic><topic>Melanoma - genetics</topic><topic>Melanoma - mortality</topic><topic>Melanoma - pathology</topic><topic>Microsatellite Repeats</topic><topic>Molecular Sequence Data</topic><topic>Monosomy - genetics</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Nucleotide sequencing</topic><topic>Phosphoproteins - genetics</topic><topic>Physiological aspects</topic><topic>Prognosis</topic><topic>Ribonucleoprotein, U2 Small Nuclear - genetics</topic><topic>Risk factors</topic><topic>RNA Splicing Factors</topic><topic>Sequence Alignment</topic><topic>Tumors</topic><topic>Uveal Neoplasms - genetics</topic><topic>Uveal Neoplasms - mortality</topic><topic>Uveal Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Martin, Marcel</creatorcontrib><creatorcontrib>Maßhöfer, Lars</creatorcontrib><creatorcontrib>Temming, Petra</creatorcontrib><creatorcontrib>Rahmann, Sven</creatorcontrib><creatorcontrib>Metz, Claudia</creatorcontrib><creatorcontrib>Bornfeld, Norbert</creatorcontrib><creatorcontrib>van de Nes, Johannes</creatorcontrib><creatorcontrib>Klein-Hitpass, Ludger</creatorcontrib><creatorcontrib>Hinnebusch, Alan G</creatorcontrib><creatorcontrib>Horsthemke, Bernhard</creatorcontrib><creatorcontrib>Lohmann, Dietmar R</creatorcontrib><creatorcontrib>Zeschnigk, Michael</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martin, Marcel</au><au>Maßhöfer, Lars</au><au>Temming, Petra</au><au>Rahmann, Sven</au><au>Metz, Claudia</au><au>Bornfeld, Norbert</au><au>van de Nes, Johannes</au><au>Klein-Hitpass, Ludger</au><au>Hinnebusch, Alan G</au><au>Horsthemke, Bernhard</au><au>Lohmann, Dietmar R</au><au>Zeschnigk, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2013-08-01</date><risdate>2013</risdate><volume>45</volume><issue>8</issue><spage>933</spage><epage>936</epage><pages>933-936</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>Michael Zeschnigk and colleagues identify recurrent somatic mutations of
EIF1AX
and
SF3B1
in uveal melanomas with disomy 3. The
EIF1AX
mutations specifically alter the N-terminal tail of the protein and were found exclusively in tumors lacking
SF3B1
mutations.
Gene expression profiles and chromosome 3 copy number divide uveal melanomas into two distinct classes correlating with prognosis
1
,
2
,
3
. Using exome sequencing, we identified recurrent somatic mutations in
EIF1AX
and
SF3B1
, specifically occurring in uveal melanomas with disomy 3, which rarely metastasize. Targeted resequencing showed that 24 of 31 tumors with disomy 3 (77%) had mutations in either
EIF1AX
(15; 48%) or
SF3B1
(9; 29%). Mutations were infrequent (2/35; 5.7%) in uveal melanomas with monosomy 3, which are associated with poor prognosis
2
. Resequencing of 13 uveal melanomas with partial monosomy 3 identified 8 tumors with a mutation in either
SF3B1
(7; 54%) or
EIF1AX
(1; 8%). All
EIF1AX
mutations caused in-frame changes affecting the N terminus of the protein, whereas 17 of 19
SF3B1
mutations encoded an alteration of Arg625. Resequencing of ten uveal melanomas with disomy 3 that developed metastases identified
SF3B1
mutations in three tumors, none of which targeted Arg625.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>23793026</pmid><doi>10.1038/ng.2674</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2013-08, Vol.45 (8), p.933-936 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4307600 |
| source | MEDLINE; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | 692/699/67/1484 Agriculture Amino Acid Sequence Aneuploidy Animal Genetics and Genomics Biomedicine Cancer Research Chromosomes, Human, Pair 3 DNA Copy Number Variations DNA sequencing Eukaryotic Initiation Factor-1 - chemistry Eukaryotic Initiation Factor-1 - genetics Exome Female Gene expression Gene Expression Profiling Gene Function Gene mutations Genetic aspects High-Throughput Nucleotide Sequencing Human Genetics Humans letter Male Melanoma Melanoma - genetics Melanoma - mortality Melanoma - pathology Microsatellite Repeats Molecular Sequence Data Monosomy - genetics Mutation Neoplasm Metastasis Nucleotide sequencing Phosphoproteins - genetics Physiological aspects Prognosis Ribonucleoprotein, U2 Small Nuclear - genetics Risk factors RNA Splicing Factors Sequence Alignment Tumors Uveal Neoplasms - genetics Uveal Neoplasms - mortality Uveal Neoplasms - pathology |
| title | Exome sequencing identifies recurrent somatic mutations in EIF1AX and SF3B1 in uveal melanoma with disomy 3 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T15%3A03%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Exome%20sequencing%20identifies%20recurrent%20somatic%20mutations%20in%20EIF1AX%20and%20SF3B1%20in%20uveal%20melanoma%20with%20disomy%203&rft.jtitle=Nature%20genetics&rft.au=Martin,%20Marcel&rft.date=2013-08-01&rft.volume=45&rft.issue=8&rft.spage=933&rft.epage=936&rft.pages=933-936&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/ng.2674&rft_dat=%3Cgale_pubme%3EA341556743%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1428036850&rft_id=info:pmid/23793026&rft_galeid=A341556743&rfr_iscdi=true |