Array-based comparative genomic hybridization for genomic-wide screening of DNA copy number alterations in aggressive bone tumors.
Array-based comparative genomic hybridization for genomic-wide screening of DNA copy number alterations in aggressive bone tumors.
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DOI：
10.1186/1756-9966-31-100
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发表时间：
2012-11-30
期刊：
影响因子：
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通讯作者：
Suzuki K
中科院分区：
文献类型：
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作者：
Kanamori M;Sano A;Yasuda T;Hori T;Suzuki K
骨肿瘤侵袭性改变的遗传途径仍然知之甚少。分析DNA拷贝数改变(DCNAs)，识别骨组织发生侵袭性改变过程中的分子事件是非常重要的。应用全基因组比较基因组杂交技术对13个侵袭性骨肿瘤(如骨巨细胞瘤、骨肉瘤等)的14个样本进行了DCNA分析，结果表明，原发性侵袭性骨肿瘤基因组拷贝数增加17.8±12.7%，287个靶克隆的拷贝数丢失17.3±11.4%(每个≦的阈值：DCNA085，1.15≦)。13例患者中有9例(7例GCT中的3例和所有恶性肿瘤)被确定为遗传不稳定病例，其定义为总DCNAs异常≧为30%。侵袭性骨肿瘤中常见的高水平扩增有转化生长因子β2、CCND3、WI6509、SHGC5557、TCL1a、CREBBP、HIC1、THRA、AFM217YD10、LAMA3、RUNX1和D22S543。另一方面，NRAS、D2S447、RAF1、Robo1、MYB、MOS、FGFR2、HRAS、D13S319、D13S327、D18S552、YES1和DCC普遍较低。在病例13中，我们比较了原发OS和其转移部位之间的遗传不稳定性。与原发病变相比，转移性病变显示有9个显著变化的DCNA增加(m/p比率≧1.3倍)。D1S214、D1S1635、EXT1、AFM137XA11、8 M16/SP6、CCND2、IgH、282 M15/SP6、HIC1和LAMA3均过表达。我们注意到了HIC1(17p13.3)，它是本系列中常见的高扩增片段。我们的结果可能为鉴定与骨肿瘤侵袭性改变相关的候选基因提供几个切入点。特别是，包括HIC1在内的17p11-13位点在P53附近是本系列和文献中常见的高扩增。
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.