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A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions

Identifieur interne : 004D69 ( PascalFrancis/Curation ); précédent : 004D68; suivant : 004D70

A 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 :

RBID : Pascal:12-0326835

Descripteurs français

English descriptors

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.
pA  
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A03   1    @0 Virchows Arch.
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A08 01  1  ENG  @1 A newly characterized human well-differentiated liposarcoma cell line contains amplifications of the 12q12-21 and 10p11-14 regions
A11 01  1    @1 PEDEUTOUR (Florence)
A11 02  1    @1 MAIRE (Georges)
A11 03  1    @1 PIERRON (Anne)
A11 04  1    @1 THOMAS (David M.)
A11 05  1    @1 GARSED (Dale W.)
A11 06  1    @1 BIANCHINI (Laurence)
A11 07  1    @1 DURANTON-TANNEUR (Valérie)
A11 08  1    @1 CORTES-MAUREL (Annabelle)
A11 09  1    @1 ITALIANO (Antoine)
A11 10  1    @1 SQUIRE (Jeremy A.)
A11 11  1    @1 COINDRE (Jean-Michel)
A14 01      @1 Institute for Research on Cancer and Aging, University of Nice-Sophia-Antipolis @2 Nice @3 FRA @Z 1 aut. @Z 3 aut. @Z 6 aut.
A14 02      @1 Laboratory of Solid Tumors Genetics, Nice University Hospital, Faculty of Medicine, 28 avenue de Valombrose @2 06107, Nice @3 FRA @Z 1 aut. @Z 7 aut. @Z 8 aut.
A14 03      @1 Department of Pathology and Molecular Medicine, Queen's University @2 Kingston, Ontario @3 CAN @Z 2 aut. @Z 10 aut.
A14 04      @1 Sarcoma Genomics and Genetics, Peter McCallum Cancer Centre @2 East Melbourne, Victoria @3 AUS @Z 4 aut. @Z 5 aut.
A14 05      @1 Department of Pathology, University of Melbourne @2 Parkville, Victoria @3 AUS @Z 5 aut.
A14 06      @1 Department of Medical Oncology, Bergonie Institute @2 Bordeaux @3 FRA @Z 9 aut.
A14 07      @1 Clinical Trials Group of the National Cancer Institute of Canada @2 Kingston, Ontario @3 CAN @Z 10 aut.
A14 08      @1 Department of Pathology, Bergonie Institute @2 Bordeaux @3 FRA @Z 11 aut.
A20       @1 67-78
A21       @1 2012
A23 01      @0 ENG
A43 01      @1 INIST @2 863 @5 354000508343660080
A44       @0 0000 @1 © 2012 INIST-CNRS. All rights reserved.
A45       @0 72 ref.
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A60       @1 P
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C01 01    ENG  @0 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.
C02 01  X    @0 002B24O
C02 02  X    @0 002B08A
C03 01  X  FRE  @0 Liposarcome @5 01
C03 01  X  ENG  @0 Liposarcoma @5 01
C03 01  X  SPA  @0 Liposarcoma @5 01
C03 02  X  FRE  @0 Homme @5 02
C03 02  X  ENG  @0 Human @5 02
C03 02  X  SPA  @0 Hombre @5 02
C03 03  X  FRE  @0 Lignée cellulaire @5 03
C03 03  X  ENG  @0 Cell line @5 03
C03 03  X  SPA  @0 Línea celular @5 03
C03 04  X  FRE  @0 Sarcome des tissus mous @2 NM @5 04
C03 04  X  ENG  @0 Soft tissue sarcoma @2 NM @5 04
C03 04  X  SPA  @0 Sarcoma de tejidos blandos @2 NM @5 04
C03 05  X  FRE  @0 Lignée cellulaire établie @5 05
C03 05  X  ENG  @0 Established cell line @5 05
C03 05  X  SPA  @0 Línea celular establecida @5 05
C03 06  X  FRE  @0 Amplification @5 06
C03 06  X  ENG  @0 Amplification @5 06
C03 06  X  SPA  @0 Amplificación @5 06
C03 07  X  FRE  @0 Chromosome C12 @5 08
C03 07  X  ENG  @0 Chromosome C12 @5 08
C03 07  X  SPA  @0 Cromosoma C12 @5 08
C03 08  X  FRE  @0 Carte génétique @5 09
C03 08  X  ENG  @0 Genetic mapping @5 09
C03 08  X  SPA  @0 Mapa genético @5 09
C03 09  X  FRE  @0 Chromosome C10 @5 11
C03 09  X  ENG  @0 Chromosome C10 @5 11
C03 09  X  SPA  @0 Cromosoma C10 @5 11
C03 10  X  FRE  @0 Gène onc cellulaire @5 12
C03 10  X  ENG  @0 C-Onc gene @5 12
C03 10  X  SPA  @0 Gen onc celular @5 12
C03 11  X  FRE  @0 Protooncogène @5 17
C03 11  X  ENG  @0 Protooncogene @5 17
C03 11  X  SPA  @0 Protooncogen @5 17
C03 12  X  FRE  @0 Gène mdm2 @5 18
C03 12  X  ENG  @0 mdm2 Gene @5 18
C03 12  X  SPA  @0 Gen mdm2 @5 18
C03 13  X  FRE  @0 Anatomopathologie @5 19
C03 13  X  ENG  @0 Anatomic pathology @5 19
C03 13  X  SPA  @0 Anatomía patológica @5 19
C07 01  X  FRE  @0 Pathologie du tissu adipeux @5 37
C07 01  X  ENG  @0 Adipose tissue disorders @5 37
C07 01  X  SPA  @0 Tejido adiposo patología @5 37
C07 02  X  FRE  @0 Tumeur maligne @2 NM @5 38
C07 02  X  ENG  @0 Malignant tumor @2 NM @5 38
C07 02  X  SPA  @0 Tumor maligno @2 NM @5 38
C07 03  X  FRE  @0 Cancer @2 NM
C07 03  X  ENG  @0 Cancer @2 NM
C07 03  X  SPA  @0 Cáncer @2 NM
N21       @1 247
N44 01      @1 OTO
N82       @1 OTO

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Pascal:12-0326835

Le document en format XML

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<name sortKey="Cortes Maurel, Annabelle" sort="Cortes Maurel, Annabelle" uniqKey="Cortes Maurel A" first="Annabelle" last="Cortes-Maurel">Annabelle Cortes-Maurel</name>
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<name sortKey="Italiano, Antoine" sort="Italiano, Antoine" uniqKey="Italiano A" first="Antoine" last="Italiano">Antoine Italiano</name>
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<country>France</country>
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<name sortKey="Squire, Jeremy A" sort="Squire, Jeremy A" uniqKey="Squire J" first="Jeremy A." last="Squire">Jeremy A. Squire</name>
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<name sortKey="Coindre, Jean Michel" sort="Coindre, Jean Michel" uniqKey="Coindre J" first="Jean-Michel" last="Coindre">Jean-Michel Coindre</name>
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<title level="j" type="main">Virchows Archiv</title>
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<idno type="ISSN">0945-6317</idno>
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<term>Amplification</term>
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<term>Chromosome C10</term>
<term>Chromosome C12</term>
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<term>Liposarcome</term>
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<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>
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