Frequent amplifications and abundant expression of TRIO , NKD2 , and IRX2 in soft tissue sarcomas

Copy number gains and high‐level amplifications of the short arm of chromosome 5 are frequently observed in soft tissue sarcomas. To identify genes from this region possibly involved in tumor progression, we analyzed 34 soft tissue sarcomas (10 pleomorphic and 8 dedifferentiated liposarcomas, 6 malignant fibrous histiocytomas, and 10 malignant peripheral nerve sheath tumors (MPNST)) using a DNA microarray including 418 BAC clones representing 99% of chromosome arm 5p. In seven tumors, distinct high‐level amplifications were identified affecting four different subregions. From these regions, genes TERT , TRIO , SKP 2 , FBXO 32 , NKD 2 , SLC 6A 3 , IRX 2 , POLS , FYB , PTGER 4 , and FGF 10 were selected for detailed quantitative expression analysis (RQ‐PCR) based on their potential tumorigenic function. Of these, TRIO , coding for a guanidine nucleotide exchange factor, was consistently overexpressed in all cases, while IRX 2 and NKD 2, both involved in the regulation of developmental processes via the WNT pathway, showed a characteristic expression only in MPNSTs. Detailed nonparametric multidimensional scaling analysis further showed that the expression of TRIO , IRX 2 , and NKD 2 strongly correlated with the gene copy number. In conclusion, we found TRIO , IRX 2 , and NKD 2 frequently affected by high‐level amplifications as well as up‐regulated in a gene‐dosage dependent manner. Thus, these genes represent candidate targets of 5p amplifications in soft tissue sarcomas and might play a crucial role during the progression of this disease. © 2006 Wiley‐Liss, Inc.