PMID- 18931480
OWN - NLM
STAT- MEDLINE
DCOM- 20081112
LR  - 20081020
IS  - 1424-859X (Electronic)
IS  - 1424-8581 (Linking)
VI  - 122
IP  - 1
DP  - 2008
TI  - Genomic signatures of chromosomal instability and osteosarcoma progression 
      detected by high resolution array CGH and interphase FISH.
PG  - 5-15
LID - 10.1159/000151310 [doi]
AB  - Osteosarcoma (OS) is characterized by an unstable karyotype which typically has a 
      heterogeneous pattern of complex chromosomal abnormalities. High-resolution array 
      comparative genomic hybridization (CGH) in combination with interphase 
      fluorescence in situ hybridization (FISH) analyses provides a complete 
      description of genomic imbalances together with an evaluation of the contribution 
      of cell-to-cell variation to copy number changes. There have been no analyses to 
      date documenting genomic signatures consistent with chromosomal instability 
      mechanisms in OS tumors using array CGH. In this study, we utilized 
      high-resolution array CGH to identify and characterize recurrent signatures of 
      genomic imbalances using ten OS tumors. Comparison between the genomic profiles 
      identified tumor groups with low, intermediate and high levels of genomic 
      imbalance. Bands 6p22-->p21, 8q24 and 17p12--> p11.2 were consistently involved 
      in high copy gain or amplification events. Since these three locations have been 
      consistently associated with OS oncogenesis, FISH probes from each cytoband were 
      used to derive an index of cellular heterogeneity for copy number within each 
      region. OS with the highest degree of genomic imbalance also exhibited the most 
      extreme cell-to-cell copy number variation. Significantly, the three OS with the 
      most imbalance and genomic copy number heterogeneity also had the poorest 
      response to preoperative chemotherapy. This genome wide analysis is the first 
      utilizing oligonucleotide array CGH in combination with FISH analysis to derive 
      genomic signatures of chromosomal instability in OS tumors by studying genomic 
      imbalance and intercellular heterogeneity. This comprehensive genomic screening 
      approach provides important insights concerning the mechanisms responsible for 
      generating complex genomes. The resulting phenotypic diversity can generate 
      tumors with a propensity for an aggressive disease course. A better understanding 
      of the underlying mechanisms leading to OS tumor development could result in the 
      identification of prognostic markers and therapeutic targets.
CI  - Copyright 2008 S. Karger AG, Basel.
FAU - Selvarajah, S
AU  - Selvarajah S
AD  - Department of Genetics and Genome Biology, The Hospital for Sick Children, 
      Toronto, Canada.
FAU - Yoshimoto, M
AU  - Yoshimoto M
FAU - Ludkovski, O
AU  - Ludkovski O
FAU - Park, P C
AU  - Park PC
FAU - Bayani, J
AU  - Bayani J
FAU - Thorner, P
AU  - Thorner P
FAU - Maire, G
AU  - Maire G
FAU - Squire, J A
AU  - Squire JA
FAU - Zielenska, M
AU  - Zielenska M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081014
PL  - Switzerland
TA  - Cytogenet Genome Res
JT  - Cytogenetic and genome research
JID - 101142708
SB  - IM
MH  - Adolescent
MH  - Bone Neoplasms/*genetics/pathology
MH  - Child
MH  - *Chromosomal Instability
MH  - Chromosomes, Artificial, Bacterial/genetics
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Chromosomes, Human, Pair 8/genetics
MH  - Female
MH  - Gene Dosage
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase/genetics
MH  - Karyotyping
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis
MH  - Osteosarcoma/*genetics/pathology
MH  - Prognosis
EDAT- 2008/10/22 09:00
MHDA- 2008/11/13 09:00
CRDT- 2008/10/22 09:00
PHST- 2008/05/23 00:00 [accepted]
PHST- 2008/10/22 09:00 [pubmed]
PHST- 2008/11/13 09:00 [medline]
PHST- 2008/10/22 09:00 [entrez]
AID - 000151310 [pii]
AID - 10.1159/000151310 [doi]
PST - ppublish
SO  - Cytogenet Genome Res. 2008;122(1):5-15. doi: 10.1159/000151310. Epub 2008 Oct 14.