Association of SV40 with human tumors.

Abstract

In 1994, PCR and protein studies suggested that SV40 DNA sequences and proteins were present in 29/48 (60%) USA human mesothelioma samples. Sequence analysis confirmed that the sequences were homologous to SV40. One year later, SV40 was also found in 5/9 human mesotheliomas, and in 1996 SV40 was also reported to be present in 1/3 of the tumor specimens examined. These reports, in combination with an earlier study in 1992 which had detected SV40 in human brain tumors, raised concerns that SV40 was associated with certain types of human tumors, specifically mesothelioma, bone, and brain tumors. These findings raised concerns, because these tumor types are the same malignancies that had been observed in animals injected with SV40. However, a study in 1996 and a presentation made at the International Mesothelioma Interest Group, IMIG in 1997 failed to detect SV40 in mesotheliomas, suggesting the possibility that laboratory artifacts, such as PCR contamination, had caused the previous positive findings. In 1997, the FDA, the NIH, and the CDC organized an international conference in Bethesda to review the literature and to address the possibility that SV40 was present in, and was possibly the cause of, some human tumors. The results of that conference were reported the same year in a meeting review in Oncogene by Carbone and colleagues. Briefly, the consensus was that before accepting the possibility that SV40 was present in human tumors, a multi-laboratory study needed to be conducted. It was recommended that a blinded multi-laboratory study be directed by an independent scientist not previously associated with the controversial reports of SV40 in human specimens. It was also recommended that this study include laboratories that had reported positive findings as well as laboratories that had failed to detect SV40 in human specimens. Since 1997, about 30 independent reports have been published on this topic, including the multi-laboratory study. Evidence in favor and against a possible association of SV40 with human cancer was reviewed at an international consensus meeting at the University of Chicago on 20, 21 April 2001, entitled "Malignant Mesothelioma: Therapeutic Options and the Role of SV40, 2001". The main focus was the association of SV40 with mesothelioma and other human tumors. At the end of the meeting, a panel discussion, which included independent experts who had not published on this topic, critically reviewed the evidence presented at the meeting. The results of the meeting and of the final panel discussion are outlined below.