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Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.

Hallor, Karolin H; Staaf, Johan LU ; Bovée, Judith V M G; Hogendoorn, Pancras C W; Cleton-Jansen, Anne-Marie; Knuutila, Sakari; Savola, Suvi; Niini, Tarja; Brosjö, Otte and Bauer, Henrik C F, et al. (2009) In Clinical Cancer Research 15(8). p.2685-2694
Abstract
PURPOSE: Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification. EXPERIMENTAL DESIGN: The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array comparative genomic hybridization. Statistical analyses were applied to evaluate the significance of alterations detected in subgroups based on clinical data, morphology, grade, tumor size, and karyotypic features. Also, the global gene expression profiles were... (More)
PURPOSE: Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification. EXPERIMENTAL DESIGN: The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array comparative genomic hybridization. Statistical analyses were applied to evaluate the significance of alterations detected in subgroups based on clinical data, morphology, grade, tumor size, and karyotypic features. Also, the global gene expression profiles were obtained in a subset of the tumors. RESULTS: Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Several apparently distinctive aberrations affecting conventional central and peripheral tumors, respectively, were identified. Although rare, recurrent amplifications were found at 8q24.21-q24.22 and 11q22.1-q22.3, and homozygous deletions of loci previously implicated in chondrosarcoma development affected the CDKN2A, EXT1, and EXT2 genes. The chromosomal imbalances in two distinct groups of predominantly near-haploid and near-triploid tumors, respectively, support the notion that polyploidization of an initially hyperhaploid/hypodiploid cell population is a common mechanism of chondrosarcoma progression. Increasing patient age as well as tumor grade were associated with adverse outcome, but no copy number imbalance affected metastasis development or tumor-associated death. CONCLUSION: Despite similarities in the overall genomic patterns, the present findings suggest that some regions are specifically altered in conventional central and peripheral tumors, respectively. (Less)
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Contribution to journal
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published
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Clinical Cancer Research
volume
15
issue
8
pages
2685 - 2694
publisher
American Association for Cancer Research
external identifiers
  • wos:000265314600014
  • pmid:19336518
  • scopus:65249118270
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-08-2330
language
English
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yes
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2d6e237b-7373-4dec-bdc7-ad68fc770ad9 (old id 1392553)
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http://www.ncbi.nlm.nih.gov/pubmed/19336518?dopt=Abstract
date added to LUP
2009-05-04 16:07:53
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2017-08-13 04:37:18
@article{2d6e237b-7373-4dec-bdc7-ad68fc770ad9,
  abstract     = {PURPOSE: Histologic grade is currently the best predictor of clinical course in chondrosarcoma patients. Grading suffers, however, from extensive interobserver variability and new objective markers are needed. Hence, we have investigated DNA copy numbers in chondrosarcomas with the purpose of identifying markers useful for prognosis and subclassification. EXPERIMENTAL DESIGN: The overall pattern of genomic imbalances was assessed in a series of 67 chondrosarcomas using array comparative genomic hybridization. Statistical analyses were applied to evaluate the significance of alterations detected in subgroups based on clinical data, morphology, grade, tumor size, and karyotypic features. Also, the global gene expression profiles were obtained in a subset of the tumors. RESULTS: Genomic imbalances, in most tumors affecting large regions of the genome, were found in 90% of the cases. Several apparently distinctive aberrations affecting conventional central and peripheral tumors, respectively, were identified. Although rare, recurrent amplifications were found at 8q24.21-q24.22 and 11q22.1-q22.3, and homozygous deletions of loci previously implicated in chondrosarcoma development affected the CDKN2A, EXT1, and EXT2 genes. The chromosomal imbalances in two distinct groups of predominantly near-haploid and near-triploid tumors, respectively, support the notion that polyploidization of an initially hyperhaploid/hypodiploid cell population is a common mechanism of chondrosarcoma progression. Increasing patient age as well as tumor grade were associated with adverse outcome, but no copy number imbalance affected metastasis development or tumor-associated death. CONCLUSION: Despite similarities in the overall genomic patterns, the present findings suggest that some regions are specifically altered in conventional central and peripheral tumors, respectively.},
  author       = {Hallor, Karolin H and Staaf, Johan and Bovée, Judith V M G and Hogendoorn, Pancras C W and Cleton-Jansen, Anne-Marie and Knuutila, Sakari and Savola, Suvi and Niini, Tarja and Brosjö, Otte and Bauer, Henrik C F and Vult von Steyern, Fredrik and Jonsson, Kjell and Skorpil, Mikael and Mandahl, Nils and Mertens, Fredrik},
  issn         = {1078-0432},
  language     = {eng},
  number       = {8},
  pages        = {2685--2694},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Genomic profiling of chondrosarcoma: chromosomal patterns in central and peripheral tumors.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-08-2330},
  volume       = {15},
  year         = {2009},
}