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Ring chromosomes, breakpoint clusters, and neocentromeres in sarcomas.

Macchia, Gemma; Hansén Nord, Karolin LU ; Zoli, Monica; Purgato, Stefania; D'Addabbo, Pietro; Whelan, Christopher W; Carbone, Lucia; Perini, Giovanni; Mertens, Fredrik LU and Rocchi, Mariano, et al. (2015) In Genes, Chromosomes and Cancer 54(3). p.156-167
Abstract
Gene amplification is relatively common in tumors. In certain subtypes of sarcoma, it often occurs in the form of ring and/or giant rod-shaped marker (RGM) chromosomes whose mitotic stability is frequently rescued by ectopic novel centromeres (neocentromeres). Little is known about the origin and structure of these RGM chromosomes, including how they arise, their internal organization, and which sequences underlie the neocentromeres. To address these questions, 42 sarcomas with RGM chromosomes were investigated to detect regions prone to double strand breaks and possible functional or structural constraints driving the amplification process. We found nine breakpoint cluster regions potentially involved in the genesis of RGM chromosomes,... (More)
Gene amplification is relatively common in tumors. In certain subtypes of sarcoma, it often occurs in the form of ring and/or giant rod-shaped marker (RGM) chromosomes whose mitotic stability is frequently rescued by ectopic novel centromeres (neocentromeres). Little is known about the origin and structure of these RGM chromosomes, including how they arise, their internal organization, and which sequences underlie the neocentromeres. To address these questions, 42 sarcomas with RGM chromosomes were investigated to detect regions prone to double strand breaks and possible functional or structural constraints driving the amplification process. We found nine breakpoint cluster regions potentially involved in the genesis of RGM chromosomes, which turned out to be significantly enriched in poly-pyrimidine traits. Some of the clusters were located close to genes already known to be relevant for sarcomas, thus indicating a potential functional constraint, while others mapped to transcriptionally inactive chromatin domains enriched in heterochromatic sites. Of note, five neocentromeres were identified after analyzing 13 of the cases by fluorescent in situ hybridization. ChIP-on-chip analysis with antibodies against the centromeric protein CENP-A showed that they were a patchwork of small genomic segments derived from different chromosomes, likely joint to form a contiguous sequence during the amplification process. © 2014 Wiley Periodicals, Inc. (Less)
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Genes, Chromosomes and Cancer
volume
54
issue
3
pages
156 - 167
publisher
John Wiley & Sons
external identifiers
  • pmid:25421174
  • wos:000348577000003
  • scopus:84921464511
ISSN
1045-2257
DOI
10.1002/gcc.22228
language
English
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yes
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301e11f0-736a-4781-a5b4-929c72a80017 (old id 4816188)
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http://www.ncbi.nlm.nih.gov/pubmed/25421174?dopt=Abstract
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2014-12-03 17:55:23
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@article{301e11f0-736a-4781-a5b4-929c72a80017,
  abstract     = {Gene amplification is relatively common in tumors. In certain subtypes of sarcoma, it often occurs in the form of ring and/or giant rod-shaped marker (RGM) chromosomes whose mitotic stability is frequently rescued by ectopic novel centromeres (neocentromeres). Little is known about the origin and structure of these RGM chromosomes, including how they arise, their internal organization, and which sequences underlie the neocentromeres. To address these questions, 42 sarcomas with RGM chromosomes were investigated to detect regions prone to double strand breaks and possible functional or structural constraints driving the amplification process. We found nine breakpoint cluster regions potentially involved in the genesis of RGM chromosomes, which turned out to be significantly enriched in poly-pyrimidine traits. Some of the clusters were located close to genes already known to be relevant for sarcomas, thus indicating a potential functional constraint, while others mapped to transcriptionally inactive chromatin domains enriched in heterochromatic sites. Of note, five neocentromeres were identified after analyzing 13 of the cases by fluorescent in situ hybridization. ChIP-on-chip analysis with antibodies against the centromeric protein CENP-A showed that they were a patchwork of small genomic segments derived from different chromosomes, likely joint to form a contiguous sequence during the amplification process. © 2014 Wiley Periodicals, Inc.},
  author       = {Macchia, Gemma and Hansén Nord, Karolin and Zoli, Monica and Purgato, Stefania and D'Addabbo, Pietro and Whelan, Christopher W and Carbone, Lucia and Perini, Giovanni and Mertens, Fredrik and Rocchi, Mariano and Storlazzi, Clelia Tiziana},
  issn         = {1045-2257},
  language     = {eng},
  number       = {3},
  pages        = {156--167},
  publisher    = {John Wiley & Sons},
  series       = {Genes, Chromosomes and Cancer},
  title        = {Ring chromosomes, breakpoint clusters, and neocentromeres in sarcomas.},
  url          = {http://dx.doi.org/10.1002/gcc.22228},
  volume       = {54},
  year         = {2015},
}