The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines
Identifieur interne : 001581 ( Istex/Corpus ); précédent : 001580; suivant : 001582The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines
Auteurs : T. A. Jones ; R. H. Flomen ; G. Senger ; D. Nižeti ; D. SheerSource :
- European Journal of Cancer [ 0959-8049 ] ; 2000.
English descriptors
- Teeft :
- Cell line, Cell lines, Chromosome, Chromosome band, Clone, Contig, Ddx1, Erythroleukaemia cell line, European journal, Gene, Genomic, Genomic clone, Hgmp resource centre, High expression, High levels, Homeobox, Homeobox gene, Homeobox genes, Hybridisation, Leukaemia, Life technologies, Medulloblastoma, Medulloblastoma cell lines, Meis1, Meis1 expression, Meis1 gene, Mrna, Mycn, Myeloid, Myeloid ecotropic integration site, Neuroblastoma, Neuroblastoma cell line, Neuroblastoma cell lines, Other neuroblastoma, Pac, Positive clones, Tumour.
Abstract
Abstract: Neuroblastoma is a childhood tumour of the sympathetic nervous system that demonstrates striking clinical heterogeneity. In order to determine which genes are abnormally expressed in neuroblastoma, we screened regions of amplification from the short arm of chromosome 2 in the neuroblastoma cell line IMR-32 and found that the homeobox gene, myeloid ecotropic integration site 1 (MEIS1), is highly amplified. MEIS1 normally maps to chromosome band 2p14. High expression of MEIS1 without amplification was also found in other neuroblastoma cell lines, with and without MYCN amplification, and in medulloblastoma and erythroleukaemia cell lines. MEIS1 is highly expressed in cerebellum and ubiquitously expressed in normal immunohaematopoietic tissues and is thought to be important in cell proliferation and differentiation. While several lines of evidence point towards a role for homeobox genes in the development of other malignancies, this is the first report showing the amplification of a homeobox gene in neuroblastoma.
Url:
DOI: 10.1016/S0959-8049(00)00332-4
Links to Exploration step
ISTEX:8B61ADE4248EFF33C6B120F0050947F7480F89D6Le document en format XML
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Senger</name><affiliation><mods:affiliation>Practice of Medical Genetics and Gynaecology, Roritzerstr. 2, 93049 Regensburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nizeti, D" sort="Nizeti, D" uniqKey="Nizeti D" first="D." last="Nižeti">D. Nižeti</name><affiliation><mods:affiliation>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</mods:affiliation></affiliation></author><author><name sortKey="Sheer, D" sort="Sheer, D" uniqKey="Sheer D" first="D." last="Sheer">D. Sheer</name><affiliation><mods:affiliation>E-mail: d.sheer@icrf.icnet.uk</mods:affiliation></affiliation><affiliation><mods:affiliation>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. 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Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</mods:affiliation></affiliation></author><author><name sortKey="Flomen, R H" sort="Flomen, R H" uniqKey="Flomen R" first="R. H." last="Flomen">R. H. Flomen</name><affiliation><mods:affiliation>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</mods:affiliation></affiliation></author><author><name sortKey="Senger, G" sort="Senger, G" uniqKey="Senger G" first="G." last="Senger">G. Senger</name><affiliation><mods:affiliation>Practice of Medical Genetics and Gynaecology, Roritzerstr. 2, 93049 Regensburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Nizeti, D" sort="Nizeti, D" uniqKey="Nizeti D" first="D." last="Nižeti">D. Nižeti</name><affiliation><mods:affiliation>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</mods:affiliation></affiliation></author><author><name sortKey="Sheer, D" sort="Sheer, D" uniqKey="Sheer D" first="D." last="Sheer">D. Sheer</name><affiliation><mods:affiliation>E-mail: d.sheer@icrf.icnet.uk</mods:affiliation></affiliation><affiliation><mods:affiliation>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">European Journal of Cancer</title><title level="j" type="abbrev">EJC</title><idno type="ISSN">0959-8049</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">36</biblScope><biblScope unit="issue">18</biblScope><biblScope unit="page" from="2368">2368</biblScope><biblScope unit="page" to="2374">2374</biblScope></imprint><idno type="ISSN">0959-8049</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0959-8049</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Cell line</term><term>Cell lines</term><term>Chromosome</term><term>Chromosome band</term><term>Clone</term><term>Contig</term><term>Ddx1</term><term>Erythroleukaemia cell line</term><term>European journal</term><term>Gene</term><term>Genomic</term><term>Genomic clone</term><term>Hgmp resource centre</term><term>High expression</term><term>High levels</term><term>Homeobox</term><term>Homeobox gene</term><term>Homeobox genes</term><term>Hybridisation</term><term>Leukaemia</term><term>Life technologies</term><term>Medulloblastoma</term><term>Medulloblastoma cell lines</term><term>Meis1</term><term>Meis1 expression</term><term>Meis1 gene</term><term>Mrna</term><term>Mycn</term><term>Myeloid</term><term>Myeloid ecotropic integration site</term><term>Neuroblastoma</term><term>Neuroblastoma cell line</term><term>Neuroblastoma cell lines</term><term>Other neuroblastoma</term><term>Pac</term><term>Positive clones</term><term>Tumour</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Neuroblastoma is a childhood tumour of the sympathetic nervous system that demonstrates striking clinical heterogeneity. In order to determine which genes are abnormally expressed in neuroblastoma, we screened regions of amplification from the short arm of chromosome 2 in the neuroblastoma cell line IMR-32 and found that the homeobox gene, myeloid ecotropic integration site 1 (MEIS1), is highly amplified. MEIS1 normally maps to chromosome band 2p14. High expression of MEIS1 without amplification was also found in other neuroblastoma cell lines, with and without MYCN amplification, and in medulloblastoma and erythroleukaemia cell lines. MEIS1 is highly expressed in cerebellum and ubiquitously expressed in normal immunohaematopoietic tissues and is thought to be important in cell proliferation and differentiation. While several lines of evidence point towards a role for homeobox genes in the development of other malignancies, this is the first report showing the amplification of a homeobox gene in neuroblastoma.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>meis1</json:string><json:string>neuroblastoma</json:string><json:string>mycn</json:string><json:string>chromosome</json:string><json:string>clone</json:string><json:string>genomic</json:string><json:string>pac</json:string><json:string>tumour</json:string><json:string>homeobox</json:string><json:string>hybridisation</json:string><json:string>medulloblastoma</json:string><json:string>neuroblastoma cell lines</json:string><json:string>ddx1</json:string><json:string>mrna</json:string><json:string>european journal</json:string><json:string>leukaemia</json:string><json:string>contig</json:string><json:string>myeloid</json:string><json:string>cell lines</json:string><json:string>homeobox genes</json:string><json:string>high levels</json:string><json:string>homeobox gene</json:string><json:string>cell line</json:string><json:string>medulloblastoma cell lines</json:string><json:string>chromosome band</json:string><json:string>myeloid ecotropic integration site</json:string><json:string>meis1 expression</json:string><json:string>high expression</json:string><json:string>meis1 gene</json:string><json:string>neuroblastoma cell line</json:string><json:string>hgmp resource centre</json:string><json:string>life technologies</json:string><json:string>erythroleukaemia cell line</json:string><json:string>positive clones</json:string><json:string>other neuroblastoma</json:string><json:string>genomic clone</json:string><json:string>gene</json:string></teeft></keywords><author><json:item><name>T.A. Jones</name><affiliations><json:string>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</json:string></affiliations></json:item><json:item><name>R.H. Flomen</name><affiliations><json:string>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</json:string></affiliations></json:item><json:item><name>G. Senger</name><affiliations><json:string>Practice of Medical Genetics and Gynaecology, Roritzerstr. 2, 93049 Regensburg, Germany</json:string></affiliations></json:item><json:item><name>D. Nižetić</name><affiliations><json:string>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</json:string></affiliations></json:item><json:item><name>D. Sheer</name><affiliations><json:string>E-mail: d.sheer@icrf.icnet.uk</json:string><json:string>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. 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In order to determine which genes are abnormally expressed in neuroblastoma, we screened regions of amplification from the short arm of chromosome 2 in the neuroblastoma cell line IMR-32 and found that the homeobox gene, myeloid ecotropic integration site 1 (MEIS1), is highly amplified. MEIS1 normally maps to chromosome band 2p14. High expression of MEIS1 without amplification was also found in other neuroblastoma cell lines, with and without MYCN amplification, and in medulloblastoma and erythroleukaemia cell lines. MEIS1 is highly expressed in cerebellum and ubiquitously expressed in normal immunohaematopoietic tissues and is thought to be important in cell proliferation and differentiation. While several lines of evidence point towards a role for homeobox genes in the development of other malignancies, this is the first report showing the amplification of a homeobox gene in neuroblastoma.</abstract><qualityIndicators><score>8.196</score><pdfWordCount>4408</pdfWordCount><pdfCharCount>27252</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>7</pdfPageCount><pdfPageSize>595 x 794 pts</pdfPageSize><refBibsNative>true</refBibsNative><abstractWordCount>149</abstractWordCount><abstractCharCount>1035</abstractCharCount><keywordCount>6</keywordCount></qualityIndicators><title>The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines</title><pmid><json:string>11094311</json:string></pmid><pii><json:string>S0959-8049(00)00332-4</json:string></pii><genre><json:string>research-article</json:string></genre><host><title>European Journal of Cancer</title><language><json:string>unknown</json:string></language><publicationDate>2000</publicationDate><issn><json:string>0959-8049</json:string></issn><pii><json:string>S0959-8049(00)X0096-2</json:string></pii><volume>36</volume><issue>18</issue><pages><first>2368</first><last>2374</last></pages><genre><json:string>journal</json:string></genre></host><namedEntities><unitex><date><json:string>2000</json:string></date><geogName></geogName><orgName><json:string>Medical Research Council</json:string><json:string>UK Centre for Applied Molecular Biology, School of Pharmacy, University of London</json:string><json:string>MJ Research, MA, USA</json:string><json:string>The Johns Hopkins Oncology Center, Baltimore</json:string><json:string>Bernhard Nocht Institute, Hamburg, Germany</json:string><json:string>Life Technologies</json:string><json:string>Biotech</json:string><json:string>Gunma University, Japan</json:string><json:string>RAD Laboratories Ltd</json:string><json:string>Elsevier Science Ltd.</json:string><json:string>Invitrogen</json:string><json:string>Clontech</json:string><json:string>Cancer Research Campaign, UK and Human Genome</json:string><json:string>Clontech Laboratories Inc., Palo Alto</json:string><json:string>Medical Research Council, UK</json:string><json:string>American Type Culture Collection</json:string><json:string>MRC</json:string><json:string>Imperial Cancer Research Fund</json:string><json:string>HGMP</json:string></orgName><orgName_funder><json:string>Imperial Cancer Research Fund</json:string><json:string>HGMP</json:string></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Groet</json:string><json:string>Pedro Baptista</json:string><json:string>T.E. 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Jones et al.</json:string><json:string>[25]</json:string><json:string>[9]</json:string><json:string>[22,23]</json:string><json:string>[2]</json:string><json:string>[27,28]</json:string><json:string>[19]</json:string></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/6H6-DHFX91T3-2</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - oncology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - oncology & carcinogenesis</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Cancer Research</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Oncology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string><json:string>4 - hemopathies</json:string></inist></categories><publicationDate>2000</publicationDate><copyrightDate>2000</copyrightDate><doi><json:string>10.1016/S0959-8049(00)00332-4</json:string></doi><id>8B61ADE4248EFF33C6B120F0050947F7480F89D6</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-DHFX91T3-2/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-DHFX91T3-2/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/6H6-DHFX91T3-2/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a">The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">ELSEVIER</publisher><availability><licence><p>©2000 Elsevier Science Ltd</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</p></availability><date>2000</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note type="content">Fig. 1: Amplification of: (a) MYCN (pNb-1); and (c) myeloid ecotropic integration site 1 (MEIS1) (I.M.A.G.E. clone 223490) along the p arm of the derivative chromosome 1 in the cell line IMR-32. Biotinylated probes were detected with avidin–fluoresceinisothiocyanate (FITC). Fluorescence in situ hybridisation (FISH) of DDX1 (lambda 2001) onto IMR-32 also showed amplification (data not shown). (b) Two-colour FISH to normal human chromosome 2 showing the order: telomere — group II (PAC 172B3) (Texas Red) — group I (PAC 2E20) (FITC) — centromere.</note><note type="content">Fig. 2: PAC contig. The scale in kb is shown at the top of the figure, with the positions of sequence tagged site (STS) markers and centromere/telomere orientation indicated above. The open bar below is a representation of genomic DNA showing the positions of XhoI (X), SalI (S) and NotI (N) restriction enzyme sites. Sizes of restriction fragments are shown by vertical lines within the open bar. The location of the MEIS1 gene is indicated directly below the open bar and genomic fragments containing gene coding sequences are marked with horizontal bars. The arrow indicates the 5′ to 3′ orientation of the gene. Brackets beneath the open bar show that the order of these XhoI sites has not been determined. The lower part of the figure comprises the PAC contig, with SP6/T7 vector ends boxed and restriction enzyme sites denoted by vertical lines attached to the PACs. The positions of the original two groups of clones are marked beneath the PAC contig.</note><note type="content">Fig. 3: Reverse transcriptase-polymerase chain reaction (RT-PCR) showing myeloid ecotropic integration site 1 (MEIS1) expression. Ubiquitous expression is shown in normal cerebellum, bone marrow and brain, the neuroblastoma cell lines (IMR-32, SK-N-AS, SK-N-FI, Kelly, SK-N-LI, SK-N-Be, SK-N-DZ and CHP212), the medulloblastoma cell lines (HTB186, TE671 and D283), an erythroleukaemia cell line (HEL 92.1.7), a chronic myeloid leukaemia cell line (K-562), a follicular thyroid carcinoma cell line (RO82-W-1) and a human lung carcinoma cell line (A549). No expression was found in the human Burkitt's lymphoma cell line (Daudi). Controls lacking cDNA (shown) and controls lacking reverse transcriptase (data not shown) were negative for all samples.</note><note type="content">Fig. 4: Northern blot analysis of myeloid ecotropic integration site 1 (MEIS1) expression in the MYCN-amplified neuroblastoma cell lines CHP212, SK-N-DZ, SK-N-Be and IMR-32 and the neuroblastoma cell line that lacks amplification, SK-N-AS. 2 μg Poly (A)+ RNA were loaded in each lane and the blot sequentially hybridised with the MEIS1 I.M.A.G.E. clone 223490, MYCN (pNb-1) and β-actin.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines</title><author xml:id="author-0000"><persName><forename type="first">T.A.</forename><surname>Jones</surname></persName><note type="biography">Joint first authors.</note><affiliation>Joint first authors.</affiliation><affiliation>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</affiliation></author><author xml:id="author-0001"><persName><forename type="first">R.H.</forename><surname>Flomen</surname></persName><note type="biography">Joint first authors.</note><affiliation>Joint first authors.</affiliation><affiliation>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</affiliation></author><author xml:id="author-0002"><persName><forename type="first">G.</forename><surname>Senger</surname></persName><affiliation>Practice of Medical Genetics and Gynaecology, Roritzerstr. 2, 93049 Regensburg, Germany</affiliation></author><author xml:id="author-0003"><persName><forename type="first">D.</forename><surname>Nižetić</surname></persName><affiliation>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</affiliation></author><author xml:id="author-0004"><persName><forename type="first">D.</forename><surname>Sheer</surname></persName><email>d.sheer@icrf.icnet.uk</email><note type="correspondence"><p>Corresponding author. Tel.: +44 20 7269 3220; fax: +44 20 7269 3655</p></note><affiliation>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</affiliation></author><idno type="istex">8B61ADE4248EFF33C6B120F0050947F7480F89D6</idno><idno type="ark">ark:/67375/6H6-DHFX91T3-2</idno><idno type="DOI">10.1016/S0959-8049(00)00332-4</idno><idno type="PII">S0959-8049(00)00332-4</idno></analytic><monogr><title level="j">European Journal of Cancer</title><title level="j" type="abbrev">EJC</title><idno type="pISSN">0959-8049</idno><idno type="PII">S0959-8049(00)X0096-2</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000"></date><biblScope unit="volume">36</biblScope><biblScope unit="issue">18</biblScope><biblScope unit="page" from="2368">2368</biblScope><biblScope unit="page" to="2374">2374</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2000</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: Neuroblastoma is a childhood tumour of the sympathetic nervous system that demonstrates striking clinical heterogeneity. In order to determine which genes are abnormally expressed in neuroblastoma, we screened regions of amplification from the short arm of chromosome 2 in the neuroblastoma cell line IMR-32 and found that the homeobox gene, myeloid ecotropic integration site 1 (MEIS1), is highly amplified. MEIS1 normally maps to chromosome band 2p14. High expression of MEIS1 without amplification was also found in other neuroblastoma cell lines, with and without MYCN amplification, and in medulloblastoma and erythroleukaemia cell lines. MEIS1 is highly expressed in cerebellum and ubiquitously expressed in normal immunohaematopoietic tissues and is thought to be important in cell proliferation and differentiation. While several lines of evidence point towards a role for homeobox genes in the development of other malignancies, this is the first report showing the amplification of a homeobox gene in neuroblastoma.</p></abstract><textClass><keywords scheme="keyword"><list><head>article-category</head><item><term>Paediatric Oncology</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>MEIS1</term></item><item><term>Neuroblastoma</term></item><item><term>IMR-32</term></item><item><term>Amplification</term></item><item><term>Expression</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2000-07-24">Modified</change><change when="2000">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-DHFX91T3-2/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>EJC</jid><aid>3659</aid><ce:pii>S0959-8049(00)00332-4</ce:pii><ce:doi>10.1016/S0959-8049(00)00332-4</ce:doi><ce:copyright type="full-transfer" year="2000">Elsevier Science Ltd</ce:copyright><ce:doctopics><ce:doctopic><ce:text>Paediatric Oncology</ce:text></ce:doctopic></ce:doctopics></item-info><head><ce:title>The homeobox gene <ce:italic>MEIS1</ce:italic> is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines</ce:title><ce:author-group><ce:author><ce:given-name>T.A.</ce:given-name><ce:surname>Jones</ce:surname><ce:cross-ref refid="FN1"><ce:sup>†</ce:sup></ce:cross-ref><ce:cross-ref refid="AFFA"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>R.H.</ce:given-name><ce:surname>Flomen</ce:surname><ce:cross-ref refid="FN1">†</ce:cross-ref><ce:cross-ref refid="AFFB"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>G.</ce:given-name><ce:surname>Senger</ce:surname><ce:cross-ref refid="AFFC"><ce:sup>c</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>D.</ce:given-name><ce:surname>Nižetić</ce:surname><ce:cross-ref refid="AFFB"><ce:sup>b</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>D.</ce:given-name><ce:surname>Sheer</ce:surname><ce:cross-ref refid="AFFA"><ce:sup>a</ce:sup></ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref><ce:e-address>d.sheer@icrf.icnet.uk</ce:e-address></ce:author><ce:affiliation id="AFFA"><ce:label>a</ce:label><ce:textfn>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</ce:textfn></ce:affiliation><ce:affiliation id="AFFB"><ce:label>b</ce:label><ce:textfn>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</ce:textfn></ce:affiliation><ce:affiliation id="AFFC"><ce:label>c</ce:label><ce:textfn>Practice of Medical Genetics and Gynaecology, Roritzerstr. 2, 93049 Regensburg, Germany</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author. Tel.: +44 20 7269 3220; fax: +44 20 7269 3655</ce:text></ce:correspondence><ce:footnote id="FN1"><ce:label>†</ce:label><ce:note-para>Joint first authors.</ce:note-para></ce:footnote></ce:author-group><ce:date-received day="13" month="4" year="2000"></ce:date-received><ce:date-revised day="24" month="7" year="2000"></ce:date-revised><ce:date-accepted day="16" month="8" year="2000"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Neuroblastoma is a childhood tumour of the sympathetic nervous system that demonstrates striking clinical heterogeneity. In order to determine which genes are abnormally expressed in neuroblastoma, we screened regions of amplification from the short arm of chromosome 2 in the neuroblastoma cell line IMR-32 and found that the homeobox gene, myeloid ecotropic integration site 1 (<ce:italic>MEIS1</ce:italic>), is highly amplified. <ce:italic>MEIS1</ce:italic> normally maps to chromosome band 2p14. High expression of <ce:italic>MEIS1</ce:italic> without amplification was also found in other neuroblastoma cell lines, with and without <ce:italic>MYCN</ce:italic> amplification, and in medulloblastoma and erythroleukaemia cell lines. <ce:italic>MEIS1</ce:italic> is highly expressed in cerebellum and ubiquitously expressed in normal immunohaematopoietic tissues and is thought to be important in cell proliferation and differentiation. While several lines of evidence point towards a role for homeobox genes in the development of other malignancies, this is the first report showing the amplification of a homeobox gene in neuroblastoma.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text><ce:italic>MEIS1</ce:italic></ce:text></ce:keyword><ce:keyword><ce:text>Neuroblastoma</ce:text></ce:keyword><ce:keyword><ce:text>IMR-32</ce:text></ce:keyword><ce:keyword><ce:text>Amplification</ce:text></ce:keyword><ce:keyword><ce:text>Expression</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>The homeobox gene MEIS1 is amplified in IMR-32 and highly expressed in other neuroblastoma cell lines</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>The homeobox gene</title></titleInfo><name type="personal"><namePart type="given">T.A.</namePart><namePart type="family">Jones</namePart><affiliation>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</affiliation><description>Joint first authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.H.</namePart><namePart type="family">Flomen</namePart><affiliation>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</affiliation><description>Joint first authors.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">G.</namePart><namePart type="family">Senger</namePart><affiliation>Practice of Medical Genetics and Gynaecology, Roritzerstr. 2, 93049 Regensburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.</namePart><namePart type="family">Nižetić</namePart><affiliation>Centre for Applied Molecular Biology, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.</namePart><namePart type="family">Sheer</namePart><affiliation>E-mail: d.sheer@icrf.icnet.uk</affiliation><affiliation>Human Cytogenetics Laboratory, Imperial Cancer Research Fund, P.O. Box 123, Lincoln's Inn Fields, London WC2A 3PX, UK</affiliation><description>Corresponding author. Tel.: +44 20 7269 3220; fax: +44 20 7269 3655</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued><dateModified encoding="w3cdtf">2000-07-24</dateModified><copyrightDate encoding="w3cdtf">2000</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: Neuroblastoma is a childhood tumour of the sympathetic nervous system that demonstrates striking clinical heterogeneity. In order to determine which genes are abnormally expressed in neuroblastoma, we screened regions of amplification from the short arm of chromosome 2 in the neuroblastoma cell line IMR-32 and found that the homeobox gene, myeloid ecotropic integration site 1 (MEIS1), is highly amplified. MEIS1 normally maps to chromosome band 2p14. High expression of MEIS1 without amplification was also found in other neuroblastoma cell lines, with and without MYCN amplification, and in medulloblastoma and erythroleukaemia cell lines. MEIS1 is highly expressed in cerebellum and ubiquitously expressed in normal immunohaematopoietic tissues and is thought to be important in cell proliferation and differentiation. While several lines of evidence point towards a role for homeobox genes in the development of other malignancies, this is the first report showing the amplification of a homeobox gene in neuroblastoma.</abstract><note type="content">Fig. 1: Amplification of: (a) MYCN (pNb-1); and (c) myeloid ecotropic integration site 1 (MEIS1) (I.M.A.G.E. clone 223490) along the p arm of the derivative chromosome 1 in the cell line IMR-32. Biotinylated probes were detected with avidin–fluoresceinisothiocyanate (FITC). Fluorescence in situ hybridisation (FISH) of DDX1 (lambda 2001) onto IMR-32 also showed amplification (data not shown). (b) Two-colour FISH to normal human chromosome 2 showing the order: telomere — group II (PAC 172B3) (Texas Red) — group I (PAC 2E20) (FITC) — centromere.</note><note type="content">Fig. 2: PAC contig. The scale in kb is shown at the top of the figure, with the positions of sequence tagged site (STS) markers and centromere/telomere orientation indicated above. The open bar below is a representation of genomic DNA showing the positions of XhoI (X), SalI (S) and NotI (N) restriction enzyme sites. Sizes of restriction fragments are shown by vertical lines within the open bar. The location of the MEIS1 gene is indicated directly below the open bar and genomic fragments containing gene coding sequences are marked with horizontal bars. The arrow indicates the 5′ to 3′ orientation of the gene. Brackets beneath the open bar show that the order of these XhoI sites has not been determined. The lower part of the figure comprises the PAC contig, with SP6/T7 vector ends boxed and restriction enzyme sites denoted by vertical lines attached to the PACs. The positions of the original two groups of clones are marked beneath the PAC contig.</note><note type="content">Fig. 3: Reverse transcriptase-polymerase chain reaction (RT-PCR) showing myeloid ecotropic integration site 1 (MEIS1) expression. Ubiquitous expression is shown in normal cerebellum, bone marrow and brain, the neuroblastoma cell lines (IMR-32, SK-N-AS, SK-N-FI, Kelly, SK-N-LI, SK-N-Be, SK-N-DZ and CHP212), the medulloblastoma cell lines (HTB186, TE671 and D283), an erythroleukaemia cell line (HEL 92.1.7), a chronic myeloid leukaemia cell line (K-562), a follicular thyroid carcinoma cell line (RO82-W-1) and a human lung carcinoma cell line (A549). No expression was found in the human Burkitt's lymphoma cell line (Daudi). Controls lacking cDNA (shown) and controls lacking reverse transcriptase (data not shown) were negative for all samples.</note><note type="content">Fig. 4: Northern blot analysis of myeloid ecotropic integration site 1 (MEIS1) expression in the MYCN-amplified neuroblastoma cell lines CHP212, SK-N-DZ, SK-N-Be and IMR-32 and the neuroblastoma cell line that lacks amplification, SK-N-AS. 2 μg Poly (A)+ RNA were loaded in each lane and the blot sequentially hybridised with the MEIS1 I.M.A.G.E. clone 223490, MYCN (pNb-1) and β-actin.</note><subject><genre>article-category</genre><topic>Paediatric Oncology</topic></subject><subject><genre>Keywords</genre><topic>MEIS1</topic><topic>Neuroblastoma</topic><topic>IMR-32</topic><topic>Amplification</topic><topic>Expression</topic></subject><relatedItem type="host"><titleInfo><title>European Journal of Cancer</title></titleInfo><titleInfo type="abbreviated"><title>EJC</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">2000</dateIssued></originInfo><identifier type="ISSN">0959-8049</identifier><identifier type="PII">S0959-8049(00)X0096-2</identifier><part><date>2000</date><detail type="volume"><number>36</number><caption>vol.</caption></detail><detail type="issue"><number>18</number><caption>no.</caption></detail><extent unit="issue-pages"><start>2277</start><end>2436</end></extent><extent unit="pages"><start>2368</start><end>2374</end></extent></part></relatedItem><identifier type="istex">8B61ADE4248EFF33C6B120F0050947F7480F89D6</identifier><identifier type="ark">ark:/67375/6H6-DHFX91T3-2</identifier><identifier type="DOI">10.1016/S0959-8049(00)00332-4</identifier><identifier type="PII">S0959-8049(00)00332-4</identifier><accessCondition type="use and reproduction" contentType="copyright">©2000 Elsevier Science Ltd</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Elsevier Science Ltd, ©2000</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-DHFX91T3-2/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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