INTEGRATION OF SV40 IN HUMAN OSTEOSARCOMA DNA

Simian virus 40 (SV40) has been demonstrated in several types of tumor s, including osteosarcoma, by polymerase chain reaction (PCR), We dete cted SV40 sequences by PCR, followed by hybridization, in nine of 35 o steosarcoma tumors and one of 11 osteosarcoma explants, PCR can detect fewer than one virus per cell but gives little detail of the gross st ructure and abundance of the virus, Analysis by Southern blotting of t otal DNA from ten osteosarcomas, positive for SV40 by PCR, found viral integration in half of these. Analysis showed integration of one to f our copies per cell of rearranged SV40. No SV40 was detectable on blot s of the remaining five SV40(+) osteosarcomas, perhaps because of the lesser sensitivity of direct hybridization. Inactivation of the p53 an d Rb tumor suppressors is a key activity of SV40 T-antigen, Unexpected ly, correlation of these findings with our prior studies indicated tha t five of ten osteosarcomas positive for SV40 DNA had mutations of p53 , and two had deleted Rb, Apparently clonal integration with pre-exist ing alteration of a tumor suppressor gene, suggests that SV40 may play a role in the final conversion to malignant osteosarcoma.