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.
METHODS: 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.
CONCLUSION: 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.