MOLECULAR ANALYSIS OF TRANSFORMING GROWTH-FACTOR-BETA IN GIANT-CELL TUMOR OF BONE

Giant cell tumor of bone (GCT) is a primary bone neoplasm with unique cytogenetic findings including telomeric associations. Elevated expression of message RNA for transforming growth factor beta (TGFbeta), but not transforming growth factor alpha (TGFalpha), has been reported in this tumor. Further investigation of GCT was undertaken to determine whether genetic loci for TGFbeta in GCT patients with and without chromosome abnormalities are altered. Due to the reported TGFbeta overexpression in GCT, qualitative and quantitative Southern blot analyses with TGFbeta1 and TGFbeta2 and an internal control probe (p3-21) were performed with tumor DNA and DNA from normal tissue on ten patients with GCT and control individuals. No obvious TGFbeta1 or TGFbeta2 gene alterations were detected. Normal copy numbers were calculated when comparing tumor and normal DNA from GCT patients as well as DNA from control individuals. Abnormal chromosome findings, including telomeric associations, marker chromosomes, double minutes, chromosome fragments, ring chromosomes (possibly representing intra-chromosome telomeric associations), and polyploid cells were observed in seven of the ten patients with GCT. Chromosomes 11, 16, 19, 20, and 21 were most commonly observed in telomeric associations, with the terminus of the long arm of chromosome 19 being the most frequent. We conclude that there are no TGFbeta1 or TGFbeta2 gene alterations detected in GCT with the methodologies described, and that telomeric associations are a reproducible cytogenetic characteristic of this neoplasm.