Virchows Archiv

, Volume 461, Issue 1, pp 67–78

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

  • Florence Pedeutour
  • Georges Maire
  • Anne Pierron
  • David M. Thomas
  • Dale W. Garsed
  • Laurence Bianchini
  • Valérie Duranton-Tanneur
  • Annabelle Cortes-Maurel
  • Antoine Italiano
  • Jeremy A. Squire
  • Jean-Michel Coindre
Original Article

DOI: 10.1007/s00428-012-1256-5

Cite this article as:
Pedeutour, F., Maire, G., Pierron, A. et al. Virchows Arch (2012) 461: 67. doi:10.1007/s00428-012-1256-5

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 12q14.3 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.

Keywords

Liposarcoma Cell line Amplification MDM2 HMGA2 MLLT10 

Supplementary material

428_2012_1256_MOESM1_ESM.doc (1.1 mb)
ESM 1(DOC 1,081 kb)

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Florence Pedeutour
    • 1
    • 2
  • Georges Maire
    • 3
  • Anne Pierron
    • 1
  • David M. Thomas
    • 4
  • Dale W. Garsed
    • 4
    • 5
  • Laurence Bianchini
    • 1
  • Valérie Duranton-Tanneur
    • 2
  • Annabelle Cortes-Maurel
    • 2
  • Antoine Italiano
    • 6
  • Jeremy A. Squire
    • 3
    • 7
  • Jean-Michel Coindre
    • 8
  1. 1.Institute for Research on Cancer and AgingUniversity of Nice-Sophia-AntipolisNiceFrance
  2. 2.Laboratory of Solid Tumors GeneticsNice University Hospital, Faculty of MedicineNice cedex 2France
  3. 3.Department of Pathology and Molecular MedicineQueen’s UniversityKingstonCanada
  4. 4.Sarcoma Genomics and GeneticsPeter McCallum Cancer CentreEast MelbourneAustralia
  5. 5.Department of PathologyUniversity of MelbourneParkvilleAustralia
  6. 6.Department of Medical OncologyBergonié InstituteBordeauxFrance
  7. 7.Clinical Trials Group of the National Cancer Institute of CanadaKingstonCanada
  8. 8.Department of PathologyBergonié InstituteBordeauxFrance

Personalised recommendations