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

Gisselsson Nord, David LU ; Pålsson, Eva LU ; Höglund, Mattias LU ; Domanski, Henryk LU ; Mertens, Fredrik LU ; Pandis, Nikos; Sciot, Raf; Dal Cin, Paola; Bridge, Julia A and Mandahl, Nils LU (2002) In Genes, Chromosomes and Cancer 33(2). p.133-140
Abstract
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... (More)
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. (Less)
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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
in
Genes, Chromosomes and Cancer
volume
33
issue
2
pages
133 - 140
publisher
John Wiley & Sons
external identifiers
  • wos:000173107000004
  • pmid:11793439
  • scopus:18244383816
ISSN
1045-2257
DOI
10.1002/gcc.1219
language
English
LU publication?
yes
id
97b7c643-cbfc-44fe-aca2-0b15f8e896c5 (old id 106634)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11793439&dopt=Abstract
date added to LUP
2007-07-06 14:50:18
date last changed
2017-10-29 03:33:25
@article{97b7c643-cbfc-44fe-aca2-0b15f8e896c5,
  abstract     = {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.},
  author       = {Gisselsson Nord, David and Pålsson, Eva and Höglund, Mattias and Domanski, Henryk and Mertens, Fredrik and Pandis, Nikos and Sciot, Raf and Dal Cin, Paola and Bridge, Julia A and Mandahl, Nils},
  issn         = {1045-2257},
  keyword      = {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},
  language     = {eng},
  number       = {2},
  pages        = {133--140},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma.},
  url          = {http://dx.doi.org/10.1002/gcc.1219},
  volume       = {33},
  year         = {2002},
}