PMID- 24070870
OWN - NLM
STAT- MEDLINE
DCOM- 20140909
LR  - 20161125
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 23
IP  - 4
DP  - 2014 Feb 15
TI  - Integrative genome and transcriptome analyses reveal two distinct types of ring 
      chromosome in soft tissue sarcomas.
PG  - 878-88
LID - 10.1093/hmg/ddt479 [doi]
AB  - 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 (FISH), 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 100 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.
FAU - Nord, Karolin H
AU  - Nord KH
AD  - Department of Clinical Genetics, University and Regional Laboratories, Skane 
      University Hospital, Lund University, 221 84 Lund, Sweden.
FAU - Macchia, Gemma
AU  - Macchia G
FAU - Tayebwa, Johnbosco
AU  - Tayebwa J
FAU - Nilsson, Jenny
AU  - Nilsson J
FAU - Vult von Steyern, Fredrik
AU  - Vult von Steyern F
FAU - Brosjo, Otte
AU  - Brosjo O
FAU - Mandahl, Nils
AU  - Mandahl N
FAU - Mertens, Fredrik
AU  - Mertens F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130926
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (HMGA2 Protein)
RN  - 0 (Retinoblastoma Protein)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cyclin-Dependent Kinase 4/genetics
MH  - Female
MH  - Gene Amplification
MH  - Gene Expression Profiling
MH  - Genetic Association Studies
MH  - Genome, Human
MH  - HMGA2 Protein/genetics
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Single Nucleotide
MH  - Proto-Oncogene Proteins c-mdm2/genetics/metabolism
MH  - Retinoblastoma Protein/genetics
MH  - *Ring Chromosomes
MH  - Sarcoma/*genetics/metabolism/mortality
MH  - Soft Tissue Neoplasms/*genetics/metabolism/mortality
MH  - *Transcriptome
EDAT- 2013/09/28 06:00
MHDA- 2014/09/10 06:00
CRDT- 2013/09/28 06:00
PHST- 2013/09/28 06:00 [entrez]
PHST- 2013/09/28 06:00 [pubmed]
PHST- 2014/09/10 06:00 [medline]
AID - ddt479 [pii]
AID - 10.1093/hmg/ddt479 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2014 Feb 15;23(4):878-88. doi: 10.1093/hmg/ddt479. Epub 2013 Sep 
      26.