Our present analysis indicated to 25 genes showing genetic instability, as target genes of aggressive bone tumors (Figure 2). Especially, the loss of NRAS was mainly observed in 10 cases (76.9%) of 13. NRAS mutations have detected prostate cancers before . However, there has been no report about the relationship between bone tumors and NRAS.
The incidence of aggressive changes of bone tissue is low. Similar to other solid tumors, malignant changes are characterized by high propensity for metastasis. Metaphase CGH studies have identified frequent gains and amplifications at 1p21-32, 1q21-24, 5p13, 6p12, 8q23-24, 8cen-q13, 17p11.2-13, 19q, and Xp21, and frequent losses at 6q16, 10p12-pter, and 10q22-q26 in OS [2, 10–13]. Recent studies have also reported that amplification at 17p11.2-ptel has been found in approximately 13-29% of high-grade OS [11, 14, 15].
In our data, the most remarkable change in metastatic tumor was occurred at increases (≧1.30) of D1S1635 (1p36.22), D1S214 (1p36.31), EXT1 (8q24.11-q24), AFM137XA11 (9p11.2), CCND2 (12p13), 8 M16/SP6 (12ptel), IGH (D14S308), HIC1 (17p13.3), 282 M15/SP16 (17ptel), and LAMA3 (18q11.2). DCNAs of p53 (17p13.1) have also increased scarcely (1.19 → 1.40), which have been suggested as an OS-related gene. As Chen, et al.  suggested, HIC1 (hypermethylated in cancer-1 located at 17p13.3) was frequent with p53 mutations in human OS. Their results indicated the importance of genes altered only through epigenetic mechanisms in cancer progression in conjunction with genetically modified tumor suppressor genes. In our study, HIC1 was also higher in the metastatic lesion than the primary site (m/p ratio =1.37 in Table 2). Therefore, we gave attention to the locus of 17p13 including HIC1 as a target gene.
Recent studies have reported that overexpression of 17p11-p12 have been linked p53 degradation [10, 16–20]. In Case #13, the gain of LLGL1, FLI (TOP3A) at 17p11-p12 have also detected. However, these two DCNAs were decreased in a metastatic sample, compared with primary tumor, which might be important in the step of metastasis. These findings support that target genes close to p53 (17p13.1), may contribute to OS tumorigenesis [17, 18].
Thus, the present pilot study suggests that array CGH could powerful means to detect genetic instability and gene aberrations that are reflected to the progression and outcome of primary aggressive bone tumors. HIC1 is increased at the both step of aggressive change and metastatic process. HIC1 might play a role of bone tumor progression and metastasis. We should pay attention the locus of 17p11-13 including HIC1, LLGL1, FLI (TOP3A), as well as p53. Further detailed studies are necessary to clarify genetic pathways of the aggressive bone tumors.