Array-comparative genomic hybridization of central chondrosarcoma: identification of ribosomal protein S6 and cyclin-dependent kinase 4 as candidate target genes for genomic aberrations.
BACKGROUND
Enchondromas are benign lesions that can occur as solitary tumors or multiple tumors (Ollier disease) and may be precursors of central chondrosarcomas. Recurrent chondrosarcomas can be of a higher grade compared with primary tumors, suggesting possible progression.


METHODS
Genome-wide array-comparative genomic hybridization (CGH) was used to investigate copy number changes in enchondromas and central chondrosarcomas to elucidate both primary genetic events and the events related to tumor progression. Analyses of variance, Student t tests, and hierarchical clustering were used for the current analyses. Array-CGH data were compared with complementary DNA (cDNA) and quantitative reverse-transcriptase polymerase chain reaction expression array data.


RESULTS
Genomic imbalances were rare in enchondromas and in grade I chondrosarcomas, whereas they were frequent in high-grade tumors. No genomic imbalances that were specific for Ollier disease were found. The authors identified 22 chromosome regions that were imbalanced in > or =25% of tumors, and 3 of those regions were located on chromosome 12 (12p13, 12p11.21-p11.23, and 12q13, containing among others the PTPRF-interacting protein-binding protein 1 (PPFIBP1) gene. Loss of chromosome 6 and gain of 12q12 were associated with higher grade. Comparison of array-CGH with cDNA expression showed correlations for the ribosomal protein S6 (RPS6) and cyclin-dependent kinase 4 (CDK4) genes.


CONCLUSIONS
In the current study the authors identified genomic regions and new candidate genes (RPS6, CDK4, and PPFIBP1) that were associated with tumor progression and prognosis in patients with high-grade chondrosarcomas.
Rozeman
Leida B
LB
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Szuhai
Karoly
K
Schrage
Yvonne M
YM
Rosenberg
Carla
C
Tanke
Hans J
HJ
Taminiau
Antonie H M
AH
Cleton-Jansen
Anne Marie
AM
Bovée
Judith V M G
JV
Hogendoorn
Pancras C W
PC
D048868:Adaptor Proteins, Signal Transducing; D001859:Bone Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D002813:Chondrosarcoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D004687:Enchondromatosis / Q000235:genetics; D005260:Female; D052138:Genes, Neoplasm; D042822:Genomic Instability; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D038601:Ribosomal Protein S6 / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C449803:PPFIBP1 protein, human; D038601:Ribosomal Protein S6; D051358:Cyclin-Dependent Kinase 4