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Array-comparative genomic hybridization of central chondrosarcoma: identification of ribosomal protein S6 and
Leida B Rozeman1, Karoly Szuhai, Yvonne M Schrage
1Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
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.
Insights
Genomic imbalances are rare in enchondromas but frequent in high-grade chondrosarcomas, indicating tumor progression. Researchers identified key genes like RPS6, CDK4, and PPFIBP1 associated with higher-grade tumors.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Enchondromas are benign bone tumors that can progress to central chondrosarcomas.
- Ollier disease involves multiple enchondromas and may have a higher risk of malignant transformation.
- Recurrent chondrosarcomas can exhibit higher grades than primary tumors, suggesting a progression pathway.
Purpose of the Study:
- To investigate copy number changes in enchondromas and central chondrosarcomas using genome-wide array-comparative genomic hybridization (array-CGH).
- To identify genetic events associated with primary tumor development and tumor progression.
- To correlate genomic imbalances with gene expression data.
Main Methods:
- Genome-wide array-comparative genomic hybridization (array-CGH) was performed on enchondromas and central chondrosarcomas.
- Statistical analyses including ANOVA and Student t tests were used to analyze copy number variations.
- Data were compared with complementary DNA (cDNA) and quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) expression data.
Main Results:
- Genomic imbalances were infrequent in enchondromas and low-grade (grade I) chondrosarcomas but common in high-grade tumors.
- No specific genomic imbalances were identified for Ollier disease.
- Twenty-two chromosome regions showed imbalances in at least 25% of tumors, including three on chromosome 12 (12p13, 12p11.21-p11.23, 12q13).
- Loss of chromosome 6 and gain of 12q12 were associated with higher tumor grade.
- Correlations between array-CGH and gene expression were observed for ribosomal protein S6 (RPS6) and cyclin-dependent kinase 4 (CDK4) genes.
Conclusions:
- Genomic regions and candidate genes (RPS6, CDK4, PPFIBP1) associated with tumor progression in high-grade chondrosarcomas were identified.
- These findings contribute to understanding the genetic basis of chondrosarcoma progression and may aid in prognosis.
- Further research into these candidate genes could reveal therapeutic targets.
