Department of Human Science, University of Toyama, 2630 Sugitani, Toyama city, Toyama 930-0194, Japan.
J Exp Clin Cancer Res. 2012 Nov 30;31(1):100. doi: 10.1186/1756-9966-31-100.
The genetic pathways of aggressive changes of bone tumors are still poorly understood. It is very important to analyze DNA copy number alterations (DCNAs), to identify the molecular events in the step of progression to the aggressive change of bone tissue.
Genome-wide array-based comparative genomic hybridization (array CGH) was used to investigate DCNAs of 14 samples from 13 aggressive bone tumors, such as giant cell tumors (GCTs) and osteosarcoma (OS), etc.
Primary aggressive bone tumors had copy number gains of 17.8±12.7% in the genome, and losses of 17.3±11.4% in 287 target clones (threshold for each DCNA: ≦085, 1.15≦). Genetic unstable cases, which were defined by the total DCNAs aberration ≧30%, were identified in 9 of 13 patients (3 of 7 GCTs and all malignant tumors). High-level amplification of TGFβ2, CCND3, WI-6509, SHGC-5557, TCL1A, CREBBP, HIC1, THRA, AFM217YD10, LAMA3, RUNX1 and D22S543, were commonly observed in aggressive bone tumors. On the other hand, NRAS, D2S447, RAF1, ROBO1, MYB, MOS, FGFR2, HRAS, D13S319, D13S327, D18S552, YES1 and DCC, were commonly low. We compared genetic instability between a primary OS and its metastatic site in Case #13. Metastatic lesion showed increased 9 DCNAs of remarkable change (m/p ratio ≧1.3 folds), compared to a primary lesion. D1S214, D1S1635, EXT1, AFM137XA11, 8 M16/SP6, CCND2, IGH, 282 M15/SP6, HIC1 and LAMA3, were overexpressed. We gave attention to HIC1 (17p13.3), which was common high amplification in this series.
Our results may provide several entry points for the identification of candidate genes associated with aggressive change of bone tumors. Especially, the locus 17p11-13 including HIC1 close to p53 was common high amplification in this series and review of the literature.
骨肿瘤侵袭性变化的遗传途径仍知之甚少。分析 DNA 拷贝数改变（DCNAs）以识别向骨组织侵袭性变化进展过程中的分子事件非常重要。
使用全基因组基于阵列的比较基因组杂交（array CGH）分析了 13 例侵袭性骨肿瘤（如巨细胞瘤（GCT）和骨肉瘤（OS）等）的 14 个样本中的 DCNAs。
原发性侵袭性骨肿瘤的基因组中存在 17.8±12.7%的拷贝数增益，287 个靶克隆中有 17.3±11.4%的缺失（每个 DCNA 的阈值：≦085，1.15≦）。通过将总 DCNAs 畸变≧30%定义为遗传不稳定病例，在 13 名患者中的 9 名（7 名 GCT 中的 3 名和所有恶性肿瘤）中确定了遗传不稳定病例。在侵袭性骨肿瘤中，经常观察到 TGFβ2、CCND3、WI-6509、SHGC-5557、TCL1A、CREBBP、HIC1、THRA、AFM217YD10、LAMA3、RUNX1 和 D22S543 的高水平扩增。另一方面，NRAS、D2S447、RAF1、ROBO1、MYB、MOS、FGFR2、HRAS、D13S319、D13S327、D18S552、YES1 和 DCC 通常低表达。我们比较了病例 13 中原发性 OS 与其转移部位之间的遗传不稳定性。与原发性病变相比，转移病变显示出 9 个显著变化的 DCNAs（m/p 比值≧1.3 倍）增加。D1S214、D1S1635、EXT1、AFM137XA11、8 M16/SP6、CCND2、IGH、282 M15/SP6、HIC1 和 LAMA3 过表达。我们关注了 HIC1（17p13.3），它在该系列中普遍高度扩增。
我们的结果可能为识别与骨肿瘤侵袭性变化相关的候选基因提供了几个切入点。特别是，包括 HIC1 在内的 17p11-13 位点靠近 p53 在本系列和文献综述中经常高度扩增。
