Presence and expression of the simian virus-40 genome in human giant cell tumors of bone

SV40 DNA sequences have been found in human tumors, such as mesotheliomas, ependymomas, and bone tumors, suggesting that SV40 may be involved in their etiology. The FOS oncogene could play an important role in bone developmen t because SV40 is able to induce FOS in cell culture. In this study, the pr esence of SV40 sequences, large T antigen (Tag), and FOS protein expression were investigated in 120 giant cell tumors (GCTs), moderately benign bone tumors that in some cases can progress to a malignant phenotype. Polymerase chain reaction (PCR), using primers that amplify the RBI pocket binding do main and the intron of Tag, was used to analyze GCT for the presence of SV4 0 DNA. Tag and FOS protein expression was evaluated by immunohistochemistry . SV40 sequences were found in 30/107 GCTs, and of these, 22/30 samples exp ressed Tag protein (73%) and 15/30 overexpressed the FOS oncogene (50%). FO S was undetectable in 77 SV40-negative GCTs. Sequence analysis of the ampli fied DNAs confirmed that the amplified sequences corresponded to SV40 DNA. The correlation between FOS overexpression and SV40-positive GCTs was highl y statistically significant (P < 0.001). These results show that SV40 DNA s equences and SV40 Tag are present in GCTs and might induce FOS activity. Th ese data suggest that SV40 might play a role in the development and progres sion of some GCTs. Genes Chromosomes Cancer 28:23-30, 2000. (C) 2000 Wiley- Liss, Inc.