Rozeman Leida B, Szuhai Karoly, Schrage Yvonne M, Rosenberg Carla, Tanke Hans J, Taminiau Antonie H M, Cleton-Jansen Anne Marie, Bovée Judith V M G, Hogendoorn Pancras C W
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Cancer. 2006 Jul 15;107(2):380-8. doi: 10.1002/cncr.22001.
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.
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.
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.
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.
内生软骨瘤是一种良性病变，可表现为孤立性肿瘤或多发性肿瘤（Ollier病），并且可能是中央型软骨肉瘤的前驱病变。与原发性肿瘤相比，复发性软骨肉瘤的分级可能更高，提示可能存在进展。
采用全基因组阵列比较基因组杂交（array-CGH）技术研究内生软骨瘤和中央型软骨肉瘤中的拷贝数变化，以阐明原发性遗传事件以及与肿瘤进展相关的事件。采用方差分析、Student t检验和层次聚类进行当前分析。将阵列CGH数据与互补DNA（cDNA）和定量逆转录聚合酶链反应表达阵列数据进行比较。
基因组失衡在内生软骨瘤和I级软骨肉瘤中罕见，而在高级别肿瘤中常见。未发现Ollier病特有的基因组失衡。作者鉴定出22个在≥25%的肿瘤中存在失衡的染色体区域，其中3个区域位于12号染色体上（12p13、12p11.21-p11.23和12q13，其中包含与PTPRF相互作用蛋白结合蛋白1（PPFIBP1）基因等）。6号染色体缺失和12q12获得与更高分级相关。将阵列CGH与cDNA表达进行比较，发现核糖体蛋白S6（RPS6）和细胞周期蛋白依赖性激酶4（CDK4）基因存在相关性。
在本研究中，作者鉴定出与高级别软骨肉瘤患者的肿瘤进展和预后相关的基因组区域和新的候选基因（RPS6、CDK4和PPFIBP1）。
