Integrative Genome and Transcriptome Analyses Reveal Two Distinct Types of Ring Chromosome in Soft Tissue Sarcomas.
Författare
Summary, in English
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.
Avdelning/ar
- Komplexa kromosomförändringar i cancer
- Genetiska avvikelser i mjukdelstumörer
- Avdelningen för klinisk genetik
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Ortopedi, Lund
Publiceringsår
2014
Språk
Engelska
Sidor
878-888
Publikation/Tidskrift/Serie
Human Molecular Genetics
Volym
23
Issue
4
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Medical Genetics
Status
Published
Forskningsgrupp
- Genetic chaos in aggressive cancer
- The genetics of soft tissue tumors
ISBN/ISSN/Övrigt
- ISSN: 0964-6906