Simian virus 40 DNA sequences in human brain and bone tumours

This report reviews recent observations regarding the association of simian virus 40 (SV40) DNA sequences with brain and bone tumours of childhood [1-3]. Our initial investigation was suggested by the tumorigenicity of SV40 in animals, and the transgenic mouse expression of SV40 large T-antigen in which all animals developed choroid plexus (CP) tumours. Polymerase chain reaction (PCR) analysis and DNA sequencing demonstrated SV40-like DNA sequences, amplified from the "Rb-pocket" binding domain of the viral large T-antigen, in 10/20 CP and 10/11 ependymoma tumours of children. The PCR analysis was subsequently extended to three additional regions of the viral genome: the carboxy-terminal region of large T-antigen, the viral enhancer/origin, and the VP1 gene. All amplified products were related to SV40 sequences. Furthermore, because one individual in the original brain tumour study was a member of a Li-Fraumeni kindred, 151 DNA samples from such families were analysed. Only 18 were positive for viral sequences and 11 of these were isolated from individuals with osteosarcomas. This observation led to a further analysis of DNA from bone tumours, in which 54/160 samples contained SV40-like sequences. These studies associate SV40-like sequences with human CP, ependymoma, and bone tumours. A causal relationship to human oncogenesis remains a subject for further study.