POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands
The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the...
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| Veröffentlicht in: | The Journal of pathology 2008-05, Vol.215 (1), p.78-86 |
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| creator | Möller, E Stenman, G Mandahl, N Hamberg, H Mölne, L van den Oord, JJ Brosjö, O Mertens, F Panagopoulos, I |
| description | The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino-terminal domain and the POU5F1 carboxy-terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild-type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/path.2327 |
| format | Article |
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POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino-terminal domain and the POU5F1 carboxy-terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild-type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><identifier>ISSN: 0022-3417</identifier><identifier>ISSN: 1096-9896</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.2327</identifier><identifier>PMID: 18338330</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Adenoma ; Adenoma, Sweat Gland - metabolism ; Adult ; Basic Medicine ; Calmodulin-Binding Proteins - genetics ; Carcinoma ; Carcinoma, Mucoepidermoid - metabolism ; Cell and Molecular Biology ; Cell- och molekylärbiologi ; Chromosome Mapping ; Chromosomes ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 6 ; dual luciferase assay ; EWSR1 ; Female ; Fluorescence ; fusion gene ; Fusion/analysis/genetics ; Genetic ; hidradenoma ; Human ; Humans ; In Situ Hybridization ; In Situ Hybridization, Fluorescence ; Medical and Health Sciences ; Medical Genetics ; MEDICIN ; Medicin och hälsovetenskap ; MEDICINE ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Middle Aged ; mucoepidermoid carcinoma ; Mucoepidermoid/metabolism ; OCT-3/4 ; Octamer Transcription Factor-3 - genetics ; Oncogene Proteins ; Oncogene Proteins, Fusion - analysis ; Oncogene Proteins, Fusion - genetics ; Pair 22 ; Pair 6 ; POU5F1 ; Pregnancy ; Reverse Transcriptase Polymerase Chain Reaction ; RNA-Binding Protein EWS ; RNA-Binding Proteins - genetics ; Salivary Glands - metabolism ; Skin Neoplasms - metabolism ; Sweat Gland/metabolism ; transcriptional activation ; Transfection - methods ; Translocation ; Translocation, Genetic</subject><ispartof>The Journal of pathology, 2008-05, Vol.215 (1), p.78-86</ispartof><rights>Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5977-f9c0e95f3d30d3a2da2530837c8f3af4a523e8da511edd819433da738f6ee33f3</citedby><cites>FETCH-LOGICAL-c5977-f9c0e95f3d30d3a2da2530837c8f3af4a523e8da511edd819433da738f6ee33f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.2327$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.2327$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,550,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18338330$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-152145$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://gup.ub.gu.se/publication/87887$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttps://lup.lub.lu.se/record/1052491$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:116953640$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Möller, E</creatorcontrib><creatorcontrib>Stenman, G</creatorcontrib><creatorcontrib>Mandahl, N</creatorcontrib><creatorcontrib>Hamberg, H</creatorcontrib><creatorcontrib>Mölne, L</creatorcontrib><creatorcontrib>van den Oord, JJ</creatorcontrib><creatorcontrib>Brosjö, O</creatorcontrib><creatorcontrib>Mertens, F</creatorcontrib><creatorcontrib>Panagopoulos, I</creatorcontrib><title>POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino-terminal domain and the POU5F1 carboxy-terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild-type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</description><subject>Adenoma</subject><subject>Adenoma, Sweat Gland - metabolism</subject><subject>Adult</subject><subject>Basic Medicine</subject><subject>Calmodulin-Binding Proteins - genetics</subject><subject>Carcinoma</subject><subject>Carcinoma, Mucoepidermoid - metabolism</subject><subject>Cell and Molecular Biology</subject><subject>Cell- och molekylärbiologi</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 22</subject><subject>Chromosomes, Human, Pair 6</subject><subject>dual luciferase assay</subject><subject>EWSR1</subject><subject>Female</subject><subject>Fluorescence</subject><subject>fusion gene</subject><subject>Fusion/analysis/genetics</subject><subject>Genetic</subject><subject>hidradenoma</subject><subject>Human</subject><subject>Humans</subject><subject>In Situ Hybridization</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Medical and Health Sciences</subject><subject>Medical Genetics</subject><subject>MEDICIN</subject><subject>Medicin och hälsovetenskap</subject><subject>MEDICINE</subject><subject>Medicinsk genetik</subject><subject>Medicinska och farmaceutiska grundvetenskaper</subject><subject>Middle Aged</subject><subject>mucoepidermoid carcinoma</subject><subject>Mucoepidermoid/metabolism</subject><subject>OCT-3/4</subject><subject>Octamer Transcription Factor-3 - genetics</subject><subject>Oncogene Proteins</subject><subject>Oncogene Proteins, Fusion - analysis</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Pair 22</subject><subject>Pair 6</subject><subject>POU5F1</subject><subject>Pregnancy</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA-Binding Protein EWS</subject><subject>RNA-Binding Proteins - genetics</subject><subject>Salivary Glands - metabolism</subject><subject>Skin Neoplasms - metabolism</subject><subject>Sweat Gland/metabolism</subject><subject>transcriptional activation</subject><subject>Transfection - methods</subject><subject>Translocation</subject><subject>Translocation, Genetic</subject><issn>0022-3417</issn><issn>1096-9896</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9ktFu0zAUhiMEYmVwwQuAr5CQms2O48S5rMq2AoVNdGXcWaexnXlN6mAnjL4LD4tDqyEuihQr1vF3Ph3p_FH0kuATgnFy2kJ3e5LQJH8UjQgusrjgRfY4GoW3JKYpyY-iZ97fYYyLgrGn0RHhlIYPj6JfV5dLdk7GSG1KK82mQoDWaoucqvoaOuuQ1ch3qkGlqmvU1r0zre0CvR0j45HuvZKos-jsZvGFILNBt0Y6kGpjGxh6u1uF_DrUYSNR05dWtUYq11gjUQmuNP-AUJsf4LaoqgPun0dPNNRevdj_j6Pl-dn1dBbPLy_eTyfzuGRFnse6KLEqmKaSYkkhkZAwijnNS64p6BRYQhWXwAhRUnJSpJRKyCnXmVKUanocxTuvv1dtvxKtM02YQlgwYl9ah5sSLGMpZoGfH-Trvg1nFc7QsCo01lRnImEpEylkUnCQTBQ0qADCcBgH3figrgq6UKr-2HjOef5f_J35OhHWVaLvBWEJSYdh3-zw1tnvvfKdaIwflgkbZXsvcpxmaZpmAXy7A0tnvXdKP5gJFkPOxJAzMeQssK_20n7VKPmX3AcrAKc74N7UanvYJK4m17O9cr8EE-L286ED3FpkOc2ZuPl8IT5-KxZT_GEmPgX-9Y7XYAVUznixXCSYUIw5J0nY8W_NtPgB</recordid><startdate>200805</startdate><enddate>200805</enddate><creator>Möller, E</creator><creator>Stenman, G</creator><creator>Mandahl, N</creator><creator>Hamberg, H</creator><creator>Mölne, L</creator><creator>van den Oord, JJ</creator><creator>Brosjö, O</creator><creator>Mertens, F</creator><creator>Panagopoulos, I</creator><general>John Wiley & Sons, Ltd</general><scope>FBQ</scope><scope>BSCLL</scope><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>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>DF2</scope><scope>F1U</scope><scope>AGCHP</scope><scope>D8T</scope><scope>D95</scope><scope>ZZAVC</scope></search><sort><creationdate>200805</creationdate><title>POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands</title><author>Möller, E ; Stenman, G ; Mandahl, N ; Hamberg, H ; Mölne, L ; van den Oord, JJ ; Brosjö, O ; Mertens, F ; Panagopoulos, I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5977-f9c0e95f3d30d3a2da2530837c8f3af4a523e8da511edd819433da738f6ee33f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenoma</topic><topic>Adenoma, Sweat Gland - metabolism</topic><topic>Adult</topic><topic>Basic Medicine</topic><topic>Calmodulin-Binding Proteins - genetics</topic><topic>Carcinoma</topic><topic>Carcinoma, Mucoepidermoid - metabolism</topic><topic>Cell and Molecular Biology</topic><topic>Cell- och molekylärbiologi</topic><topic>Chromosome Mapping</topic><topic>Chromosomes</topic><topic>Chromosomes, Human, Pair 22</topic><topic>Chromosomes, Human, Pair 6</topic><topic>dual luciferase assay</topic><topic>EWSR1</topic><topic>Female</topic><topic>Fluorescence</topic><topic>fusion gene</topic><topic>Fusion/analysis/genetics</topic><topic>Genetic</topic><topic>hidradenoma</topic><topic>Human</topic><topic>Humans</topic><topic>In Situ Hybridization</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Medical and Health Sciences</topic><topic>Medical Genetics</topic><topic>MEDICIN</topic><topic>Medicin och hälsovetenskap</topic><topic>MEDICINE</topic><topic>Medicinsk genetik</topic><topic>Medicinska och farmaceutiska grundvetenskaper</topic><topic>Middle Aged</topic><topic>mucoepidermoid carcinoma</topic><topic>Mucoepidermoid/metabolism</topic><topic>OCT-3/4</topic><topic>Octamer Transcription Factor-3 - genetics</topic><topic>Oncogene Proteins</topic><topic>Oncogene Proteins, Fusion - analysis</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Pair 22</topic><topic>Pair 6</topic><topic>POU5F1</topic><topic>Pregnancy</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA-Binding Protein EWS</topic><topic>RNA-Binding Proteins - genetics</topic><topic>Salivary Glands - metabolism</topic><topic>Skin Neoplasms - metabolism</topic><topic>Sweat Gland/metabolism</topic><topic>transcriptional activation</topic><topic>Transfection - methods</topic><topic>Translocation</topic><topic>Translocation, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Möller, E</creatorcontrib><creatorcontrib>Stenman, G</creatorcontrib><creatorcontrib>Mandahl, N</creatorcontrib><creatorcontrib>Hamberg, H</creatorcontrib><creatorcontrib>Mölne, L</creatorcontrib><creatorcontrib>van den Oord, JJ</creatorcontrib><creatorcontrib>Brosjö, O</creatorcontrib><creatorcontrib>Mertens, F</creatorcontrib><creatorcontrib>Panagopoulos, I</creatorcontrib><collection>AGRIS</collection><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Uppsala universitet</collection><collection>SWEPUB Göteborgs universitet</collection><collection>SWEPUB Lunds universitet full text</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Lunds universitet</collection><collection>SwePub Articles full text</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Möller, E</au><au>Stenman, G</au><au>Mandahl, N</au><au>Hamberg, H</au><au>Mölne, L</au><au>van den Oord, JJ</au><au>Brosjö, O</au><au>Mertens, F</au><au>Panagopoulos, I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>2008-05</date><risdate>2008</risdate><volume>215</volume><issue>1</issue><spage>78</spage><epage>86</epage><pages>78-86</pages><issn>0022-3417</issn><issn>1096-9896</issn><eissn>1096-9896</eissn><abstract>The EWSR1 gene is known to play a crucial role in the development of a number of different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is expressed during early development to maintain the totipotent status of embryonic stem and germ cells. In the present study, we report the fusion of EWSR1 and POU5F1 in two types of epithelial tumours: hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands. This finding not only broadens considerably the spectrum of neoplasms associated with EWSR1 fusion genes but also strengthens the evidence for shared pathogenetic mechanisms in the development of adnexal and salivary gland tumours. Reminiscent of the previously reported fusion genes involving EWSR1, the identified transcript is predicted to encode a chimeric protein consisting of the EWSR1 amino-terminal domain and the POU5F1 carboxy-terminal domain. We assessed the transcriptional activation potential of the chimera compared to the wild-type proteins, as well as activation of transcription through the oct/sox composite element known to bind POU5F1. Among other POU5F1 target genes, this element is present in the promoter of NANOG and in the distal enhancer of POU5F1 itself. Our results show that although the chimera is capable of significant transcriptional activation, it may in fact convey a negative regulatory effect on target genes. Copyright © 2008 Pathological Society of Great Britain and Ireland. 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| ispartof | The Journal of pathology, 2008-05, Vol.215 (1), p.78-86 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; SWEPUB Freely available online |
| subjects | Adenoma Adenoma, Sweat Gland - metabolism Adult Basic Medicine Calmodulin-Binding Proteins - genetics Carcinoma Carcinoma, Mucoepidermoid - metabolism Cell and Molecular Biology Cell- och molekylärbiologi Chromosome Mapping Chromosomes Chromosomes, Human, Pair 22 Chromosomes, Human, Pair 6 dual luciferase assay EWSR1 Female Fluorescence fusion gene Fusion/analysis/genetics Genetic hidradenoma Human Humans In Situ Hybridization In Situ Hybridization, Fluorescence Medical and Health Sciences Medical Genetics MEDICIN Medicin och hälsovetenskap MEDICINE Medicinsk genetik Medicinska och farmaceutiska grundvetenskaper Middle Aged mucoepidermoid carcinoma Mucoepidermoid/metabolism OCT-3/4 Octamer Transcription Factor-3 - genetics Oncogene Proteins Oncogene Proteins, Fusion - analysis Oncogene Proteins, Fusion - genetics Pair 22 Pair 6 POU5F1 Pregnancy Reverse Transcriptase Polymerase Chain Reaction RNA-Binding Protein EWS RNA-Binding Proteins - genetics Salivary Glands - metabolism Skin Neoplasms - metabolism Sweat Gland/metabolism transcriptional activation Transfection - methods Translocation Translocation, Genetic |
| title | POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands |
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