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Integrative Genome and Transcriptome Analyses Reveal Two Distinct Types of Ring Chromosome in Soft Tissue Sarcomas.

Hansén Nord, Karolin LU ; Macchia, Gemma; Tayebwa, Johnbosco LU ; Nilsson, Jenny LU ; Vult von Steyern, Fredrik LU ; Brosjö, Otte; Mandahl, Nils LU and Mertens, Fredrik LU (2014) In Human Molecular Genetics 23(4). p.878-888
Abstract
Gene amplification is a common phenomenon in malignant neoplasms of all types. One mechanism behind increased gene copy number is the formation of ring chromosomes. Such structures are mitotically unstable and during tumor progression they accumulate material from many different parts of the genome. Hence, their content varies considerably between and within tumors. Partly due to this extensive variation, the genetic content of many ring-containing tumors remains poorly characterized. Ring chromosomes are particularly prevalent in specific subtypes of sarcoma. Here, we have combined fluorescence in situ hybridization, global genomic copy number and gene expression data on ring-containing soft tissue sarcomas and show that they harbor two... (More)
Gene amplification is a common phenomenon in malignant neoplasms of all types. One mechanism behind increased gene copy number is the formation of ring chromosomes. Such structures are mitotically unstable and during tumor progression they accumulate material from many different parts of the genome. Hence, their content varies considerably between and within tumors. Partly due to this extensive variation, the genetic content of many ring-containing tumors remains poorly characterized. Ring chromosomes are particularly prevalent in specific subtypes of sarcoma. Here, we have combined fluorescence in situ hybridization, global genomic copy number and gene expression data on ring-containing soft tissue sarcomas and show that they harbor two fundamentally different types of ring chromosome: MDM2-positive and MDM2-negative rings. While the former are often found in an otherwise normal chromosome complement, the latter seem to arise in the context of general chromosomal instability. In line with this, sarcomas with MDM2-negative rings commonly show complete loss of either CDKN2A or RB1-both known to be important for genome integrity. Sarcomas with MDM2-positive rings instead show co-amplification of a variety of potential driver oncogenes. More than one hundred different genes were found to be involved, many of which are known to induce cell growth, promote proliferation or inhibit apoptosis. Several of the amplified and overexpressed genes constitute potential drug targets. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
23
issue
4
pages
878 - 888
publisher
Oxford University Press
external identifiers
  • pmid:24070870
  • wos:000330842100004
  • scopus:84892960740
ISSN
0964-6906
DOI
10.1093/hmg/ddt479
language
English
LU publication?
yes
id
a327c40a-62fd-40fd-b1bf-4e0175bb6476 (old id 4065349)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24070870?dopt=Abstract
date added to LUP
2013-10-03 22:17:33
date last changed
2017-07-09 03:09:25
@article{a327c40a-62fd-40fd-b1bf-4e0175bb6476,
  abstract     = {Gene amplification is a common phenomenon in malignant neoplasms of all types. One mechanism behind increased gene copy number is the formation of ring chromosomes. Such structures are mitotically unstable and during tumor progression they accumulate material from many different parts of the genome. Hence, their content varies considerably between and within tumors. Partly due to this extensive variation, the genetic content of many ring-containing tumors remains poorly characterized. Ring chromosomes are particularly prevalent in specific subtypes of sarcoma. Here, we have combined fluorescence in situ hybridization, global genomic copy number and gene expression data on ring-containing soft tissue sarcomas and show that they harbor two fundamentally different types of ring chromosome: MDM2-positive and MDM2-negative rings. While the former are often found in an otherwise normal chromosome complement, the latter seem to arise in the context of general chromosomal instability. In line with this, sarcomas with MDM2-negative rings commonly show complete loss of either CDKN2A or RB1-both known to be important for genome integrity. Sarcomas with MDM2-positive rings instead show co-amplification of a variety of potential driver oncogenes. More than one hundred different genes were found to be involved, many of which are known to induce cell growth, promote proliferation or inhibit apoptosis. Several of the amplified and overexpressed genes constitute potential drug targets.},
  author       = {Hansén Nord, Karolin and Macchia, Gemma and Tayebwa, Johnbosco and Nilsson, Jenny and Vult von Steyern, Fredrik and Brosjö, Otte and Mandahl, Nils and Mertens, Fredrik},
  issn         = {0964-6906},
  language     = {eng},
  number       = {4},
  pages        = {878--888},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Integrative Genome and Transcriptome Analyses Reveal Two Distinct Types of Ring Chromosome in Soft Tissue Sarcomas.},
  url          = {http://dx.doi.org/10.1093/hmg/ddt479},
  volume       = {23},
  year         = {2014},
}