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Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma.

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Author

Summary, in English

Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors. Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.

Publishing year

2002

Language

English

Pages

133-140

Publication/Series

Genes, Chromosomes and Cancer

Volume

33

Issue

2

Document type

Journal article

Publisher

John Wiley & Sons Inc.

Topic

  • Cancer and Oncology
  • Medical Genetics

Keywords

  • Karyotyping
  • Interphase/genetics
  • Fluorescence
  • In Situ Hybridization
  • Human
  • Gene Amplification/*genetics
  • Female
  • Comparative Study
  • Pair 12/*genetics
  • Chromosomes
  • Chromosome Banding
  • Child
  • Bone Neoplasms/*genetics/pathology
  • Base Sequence
  • Adolescence
  • Adult
  • Male
  • Metaphase/genetics
  • Middle Age
  • Osteosarcoma/*genetics/pathology
  • Support
  • Non-U.S. Gov't
  • Tumor Cells
  • Cultured

Status

Published

ISBN/ISSN/Other

  • ISSN: 1045-2257