A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions
Identifieur interne : 005F09 ( Main/Exploration ); précédent : 005F08; suivant : 005F10A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions
Auteurs : Florence Pedeutour [France] ; Georges Maire [Canada] ; Anne Pierron [France] ; David M. Thomas [Australie] ; Dale W. Garsed [Australie] ; Laurence Bianchini [France] ; Valérie Duranton-Tanneur [France] ; Annabelle Cortes-Maurel [France] ; Antoine Italiano [France] ; Jeremy A. Squire [Canada] ; Jean-Michel Coindre [France]Source :
- Virchows Archiv [ 0945-6317 ] ; 2012.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
While surgery is the usual treatment for localized well-differentiated and dedifferentiated liposarcomas (WDLPS/DDLPS), the therapeutic options for patients with advanced disease are limited. The classical antimitotic treatments are most often inefficient. The establishment of genetically characterized cell lines is therefore crucial for providing in vitro models for novel targeted therapies. We have used spectral karyotyping, fluorescence in situ hybridization with whole chromosome painting and locus-specific probes, and array-comparative genomic hybridization to identify the chromosomal and molecular alterations of a novel cell line established from a recurring sclerosing WDLPS. The karyotype was hypertriploid and showed multiple structural anomalies. All cells retained the presence of a giant marker chromosome that had been previously identified in the primary cell cultures. This giant chromosome contained high-level amplification of chromosomal regions 12q13-21 and lacked the alpha-satellite centromeric sequences associated with WDLPS/DDLPS. The 12q amplicon was large, containing 370 amplified genes. The DNA copy number ranged from 3 to 57. The highest levels of amplification were observed at 12ql4.3 for GNS, WIF1, and HMGA2. We analyzed the mRNA expression status by real-time reverse transcription polymerase chain reaction for six genes from this amplicon: MDM2, HMGA2, CDK4, TSPAN31, WIF1, and YEATS4. mRNA overexpression was correlated with genomic amplification. A second amplicon originating from 10p11-14 was also present in the giant marker chromosome. The 10p amplicon contained 62 genes, including oncogenes such as MLLT10, previously described in chimeric fusion with MLL in leukemias, NEBL, and BMI1.
Affiliations:
- Australie, Canada, France
- Aquitaine, Nouvelle-Aquitaine, Provence-Alpes-Côte d'Azur, Victoria (État)
- Bordeaux, Melbourne, Nice
- Université de Melbourne
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions</title><author><name sortKey="Pedeutour, Florence" sort="Pedeutour, Florence" uniqKey="Pedeutour F" first="Florence" last="Pedeutour">Florence Pedeutour</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute for Research on Cancer and Aging, University of Nice-Sophia-Antipolis</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Laboratory of Solid Tumors Genetics, Nice University Hospital, Faculty of Medicine, 28 avenue de Valombrose</s1><s2>06107, Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Maire, Georges" sort="Maire, Georges" uniqKey="Maire G" first="Georges" last="Maire">Georges Maire</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Pathology and Molecular Medicine, Queen's University</s1><s2>Kingston, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Kingston, Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Pierron, Anne" sort="Pierron, Anne" uniqKey="Pierron A" first="Anne" last="Pierron">Anne Pierron</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute for Research on Cancer and Aging, University of Nice-Sophia-Antipolis</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Thomas, David M" sort="Thomas, David M" uniqKey="Thomas D" first="David M." last="Thomas">David M. Thomas</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Sarcoma Genomics and Genetics, Peter McCallum Cancer Centre</s1><s2>East Melbourne, Victoria</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne, Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Garsed, Dale W" sort="Garsed, Dale W" uniqKey="Garsed D" first="Dale W." last="Garsed">Dale W. 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Squire</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Pathology and Molecular Medicine, Queen's University</s1><s2>Kingston, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Kingston, Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Clinical Trials Group of the National Cancer Institute of Canada</s1><s2>Kingston, Ontario</s2><s3>CAN</s3><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Clinical Trials Group of the National Cancer Institute of Canada</wicri:noRegion></affiliation></author><author><name sortKey="Coindre, Jean Michel" sort="Coindre, Jean Michel" uniqKey="Coindre J" first="Jean-Michel" last="Coindre">Jean-Michel Coindre</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Department of Pathology, Bergonie Institute</s1><s2>Bordeaux</s2><s3>FRA</s3><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0326835</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0326835 INIST</idno><idno type="RBID">Pascal:12-0326835</idno><idno type="wicri:Area/PascalFrancis/Corpus">001148</idno><idno type="wicri:Area/PascalFrancis/Curation">004D69</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">001405</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">001405</idno><idno type="wicri:doubleKey">0945-6317:2012:Pedeutour F:a:newly:characterized</idno><idno type="wicri:Area/Main/Merge">006240</idno><idno type="wicri:Area/Main/Curation">005F09</idno><idno type="wicri:Area/Main/Exploration">005F09</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions</title><author><name sortKey="Pedeutour, Florence" sort="Pedeutour, Florence" uniqKey="Pedeutour F" first="Florence" last="Pedeutour">Florence Pedeutour</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute for Research on Cancer and Aging, University of Nice-Sophia-Antipolis</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Laboratory of Solid Tumors Genetics, Nice University Hospital, Faculty of Medicine, 28 avenue de Valombrose</s1><s2>06107, Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Maire, Georges" sort="Maire, Georges" uniqKey="Maire G" first="Georges" last="Maire">Georges Maire</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Pathology and Molecular Medicine, Queen's University</s1><s2>Kingston, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Kingston, Ontario</wicri:noRegion></affiliation></author><author><name sortKey="Pierron, Anne" sort="Pierron, Anne" uniqKey="Pierron A" first="Anne" last="Pierron">Anne Pierron</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute for Research on Cancer and Aging, University of Nice-Sophia-Antipolis</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Thomas, David M" sort="Thomas, David M" uniqKey="Thomas D" first="David M." last="Thomas">David M. Thomas</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Sarcoma Genomics and Genetics, Peter McCallum Cancer Centre</s1><s2>East Melbourne, Victoria</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne, Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Garsed, Dale W" sort="Garsed, Dale W" uniqKey="Garsed D" first="Dale W." last="Garsed">Dale W. Garsed</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Sarcoma Genomics and Genetics, Peter McCallum Cancer Centre</s1><s2>East Melbourne, Victoria</s2><s3>AUS</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>East Melbourne, Victoria</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department of Pathology, University of Melbourne</s1><s2>Parkville, Victoria</s2><s3>AUS</s3><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Bianchini, Laurence" sort="Bianchini, Laurence" uniqKey="Bianchini L" first="Laurence" last="Bianchini">Laurence Bianchini</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Institute for Research on Cancer and Aging, University of Nice-Sophia-Antipolis</s1><s2>Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Duranton Tanneur, Valerie" sort="Duranton Tanneur, Valerie" uniqKey="Duranton Tanneur V" first="Valérie" last="Duranton-Tanneur">Valérie Duranton-Tanneur</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Laboratory of Solid Tumors Genetics, Nice University Hospital, Faculty of Medicine, 28 avenue de Valombrose</s1><s2>06107, Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Cortes Maurel, Annabelle" sort="Cortes Maurel, Annabelle" uniqKey="Cortes Maurel A" first="Annabelle" last="Cortes-Maurel">Annabelle Cortes-Maurel</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Laboratory of Solid Tumors Genetics, Nice University Hospital, Faculty of Medicine, 28 avenue de Valombrose</s1><s2>06107, Nice</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Nice</settlement></placeName></affiliation></author><author><name sortKey="Italiano, Antoine" sort="Italiano, Antoine" uniqKey="Italiano A" first="Antoine" last="Italiano">Antoine Italiano</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Department of Medical Oncology, Bergonie Institute</s1><s2>Bordeaux</s2><s3>FRA</s3><sZ>9 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author><author><name sortKey="Squire, Jeremy A" sort="Squire, Jeremy A" uniqKey="Squire J" first="Jeremy A." last="Squire">Jeremy A. Squire</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Pathology and Molecular Medicine, Queen's University</s1><s2>Kingston, Ontario</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Kingston, Ontario</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Clinical Trials Group of the National Cancer Institute of Canada</s1><s2>Kingston, Ontario</s2><s3>CAN</s3><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Clinical Trials Group of the National Cancer Institute of Canada</wicri:noRegion></affiliation></author><author><name sortKey="Coindre, Jean Michel" sort="Coindre, Jean Michel" uniqKey="Coindre J" first="Jean-Michel" last="Coindre">Jean-Michel Coindre</name><affiliation wicri:level="3"><inist:fA14 i1="08"><s1>Department of Pathology, Bergonie Institute</s1><s2>Bordeaux</s2><s3>FRA</s3><sZ>11 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Nouvelle-Aquitaine</region><region type="old region">Aquitaine</region><settlement type="city">Bordeaux</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Virchows Archiv</title><title level="j" type="abbreviated">Virchows Arch.</title><idno type="ISSN">0945-6317</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Virchows Archiv</title><title level="j" type="abbreviated">Virchows Arch.</title><idno type="ISSN">0945-6317</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Amplification</term><term>Anatomic pathology</term><term>C-Onc gene</term><term>Cell line</term><term>Chromosome C10</term><term>Chromosome C12</term><term>Established cell line</term><term>Genetic mapping</term><term>Human</term><term>Liposarcoma</term><term>Protooncogene</term><term>Soft tissue sarcoma</term><term>mdm2 Gene</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Liposarcome</term><term>Homme</term><term>Lignée cellulaire</term><term>Sarcome des tissus mous</term><term>Lignée cellulaire établie</term><term>Amplification</term><term>Chromosome C12</term><term>Carte génétique</term><term>Chromosome C10</term><term>Gène onc cellulaire</term><term>Protooncogène</term><term>Gène mdm2</term><term>Anatomopathologie</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">While surgery is the usual treatment for localized well-differentiated and dedifferentiated liposarcomas (WDLPS/DDLPS), the therapeutic options for patients with advanced disease are limited. The classical antimitotic treatments are most often inefficient. The establishment of genetically characterized cell lines is therefore crucial for providing in vitro models for novel targeted therapies. We have used spectral karyotyping, fluorescence in situ hybridization with whole chromosome painting and locus-specific probes, and array-comparative genomic hybridization to identify the chromosomal and molecular alterations of a novel cell line established from a recurring sclerosing WDLPS. The karyotype was hypertriploid and showed multiple structural anomalies. All cells retained the presence of a giant marker chromosome that had been previously identified in the primary cell cultures. This giant chromosome contained high-level amplification of chromosomal regions 12q13-21 and lacked the alpha-satellite centromeric sequences associated with WDLPS/DDLPS. The 12q amplicon was large, containing 370 amplified genes. The DNA copy number ranged from 3 to 57. The highest levels of amplification were observed at 12ql4.3 for GNS, WIF1, and HMGA2. We analyzed the mRNA expression status by real-time reverse transcription polymerase chain reaction for six genes from this amplicon: MDM2, HMGA2, CDK4, TSPAN31, WIF1, and YEATS4. mRNA overexpression was correlated with genomic amplification. A second amplicon originating from 10p11-14 was also present in the giant marker chromosome. The 10p amplicon contained 62 genes, including oncogenes such as MLLT10, previously described in chimeric fusion with MLL in leukemias, NEBL, and BMI1.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Canada</li><li>France</li></country><region><li>Aquitaine</li><li>Nouvelle-Aquitaine</li><li>Provence-Alpes-Côte d'Azur</li><li>Victoria (État)</li></region><settlement><li>Bordeaux</li><li>Melbourne</li><li>Nice</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Pedeutour, Florence" sort="Pedeutour, Florence" uniqKey="Pedeutour F" first="Florence" last="Pedeutour">Florence Pedeutour</name></region><name sortKey="Bianchini, Laurence" sort="Bianchini, Laurence" uniqKey="Bianchini L" first="Laurence" last="Bianchini">Laurence Bianchini</name><name sortKey="Coindre, Jean Michel" sort="Coindre, Jean Michel" uniqKey="Coindre J" first="Jean-Michel" last="Coindre">Jean-Michel Coindre</name><name sortKey="Cortes Maurel, Annabelle" sort="Cortes Maurel, Annabelle" uniqKey="Cortes Maurel A" first="Annabelle" last="Cortes-Maurel">Annabelle Cortes-Maurel</name><name sortKey="Duranton Tanneur, Valerie" sort="Duranton Tanneur, Valerie" uniqKey="Duranton Tanneur V" first="Valérie" last="Duranton-Tanneur">Valérie Duranton-Tanneur</name><name sortKey="Italiano, Antoine" sort="Italiano, Antoine" uniqKey="Italiano A" first="Antoine" last="Italiano">Antoine Italiano</name><name sortKey="Pedeutour, Florence" sort="Pedeutour, Florence" uniqKey="Pedeutour F" first="Florence" last="Pedeutour">Florence Pedeutour</name><name sortKey="Pierron, Anne" sort="Pierron, Anne" uniqKey="Pierron A" first="Anne" last="Pierron">Anne Pierron</name></country><country name="Canada"><noRegion><name sortKey="Maire, Georges" sort="Maire, Georges" uniqKey="Maire G" first="Georges" last="Maire">Georges Maire</name></noRegion><name sortKey="Squire, Jeremy A" sort="Squire, Jeremy A" uniqKey="Squire J" first="Jeremy A." last="Squire">Jeremy A. Squire</name><name sortKey="Squire, Jeremy A" sort="Squire, Jeremy A" uniqKey="Squire J" first="Jeremy A." last="Squire">Jeremy A. Squire</name></country><country name="Australie"><noRegion><name sortKey="Thomas, David M" sort="Thomas, David M" uniqKey="Thomas D" first="David M." last="Thomas">David M. Thomas</name></noRegion><name sortKey="Garsed, Dale W" sort="Garsed, Dale W" uniqKey="Garsed D" first="Dale W." last="Garsed">Dale W. Garsed</name><name sortKey="Garsed, Dale W" sort="Garsed, Dale W" uniqKey="Garsed D" first="Dale W." last="Garsed">Dale W. Garsed</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|wiki= Wicri/Asie
|area= AustralieFrV1
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|clé= Pascal:12-0326835
|texte= A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions
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