| Summary: | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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 <it>TGFβ2</it>, <it>CCND3</it>, <it>WI-6509</it>, <it>SHGC-5557</it>, <it>TCL1A</it>, <it>CREBBP</it>, <it>HIC1</it>, <it>THRA</it>, <it>AFM217YD10</it>, <it>LAMA3</it>, <it>RUNX1</it> and <it>D22S543</it>, were commonly observed in aggressive bone tumors. On the other hand, <it>NRAS</it>, <it>D2S447</it>, <it>RAF1</it>, <it>ROBO1</it>, <it>MYB</it>, <it>MOS</it>, <it>FGFR2</it>, <it>HRAS</it>, <it>D13S319</it>, <it>D13S327</it>, <it>D18S552</it>, <it>YES1</it> and <it>DCC</it>, 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. <it>D1S214, D1S1635, EXT1, AFM137XA11, 8 M16/SP6, CCND2, IGH, 282 M15/SP6, HIC1</it> and <it>LAMA3,</it> were overexpressed. We gave attention to <it>HIC1</it> (17p13.3), which was common high amplification in this series.</p> <p>Conclusion</p> <p>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 <it>HIC1</it> close to <it>p53</it> was common high amplification in this series and review of the literature.</p>
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